{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T16:29:47Z","timestamp":1747153787802,"version":"3.40.5"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsmedizin Rostock"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pflugers Arch - Eur J Physiol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motility of detrusor smooth muscle includes adrenergic relaxation and cholinergic contraction. Since the latter may be deregulated in overactive bladder (OAB) pathophysiology, anticholinergics are the standard therapy but occasionally less tolerated due to side effects such as dry mouth and constipation. \u03b2<jats:sub>3<\/jats:sub> adrenoceptor agonists also alleviate OAB symptoms by relaxing the detrusor muscle. Their age dependence, however, is far from understood. To address this issue, we induced contractions with KCl (60 mM) and carbachol (from 10 nM to 100 \u03bcM) in the presence of the \u03b2<jats:sub>3<\/jats:sub> adrenoceptor agonist CL316,243 (from 0.1 to 10 \u03bcM) in both human and rat muscle strips. Our results confirmed that both contractions were attenuated by \u03b2<jats:sub>3<\/jats:sub> adrenoceptor activation in both species, but with differing age dependence. In humans, specimens from mid-life subjects showed a significantly more pronounced effect of CL316,243 in attenuating carbachol-induced contractions than those from aged subjects (Cohen\u2019s d of maximal attenuation: 1.82 in mid-life versus 0.13 in aged) without altering EC<jats:sub>50<\/jats:sub>. Conversely, attenuation of KCl responses by CL316,243 increased during ageing (Spearman correlation coefficient = -0.584, <jats:italic>P<\/jats:italic>&lt;0.01). In rats, both KCl- and carbachol-induced contractions were significantly more attenuated by CL316,243 in samples from adolescent as compared to aged samples. Immunohistochemistry in human detrusor sections proved \u03b2<jats:sub>3<\/jats:sub> adrenoreceptor abundance to remain unaltered during ageing. In conclusion, our findings suggest differential age-dependent changes in human \u03b2<jats:sub>3<\/jats:sub> adrenoceptor-dependent attenuation of detrusor contraction in terms of electromechanical versus pharmacomechanical coupling; they may help understand the differential responsiveness of OAB patients to \u03b2<jats:sub>3<\/jats:sub> agents.<\/jats:p>","DOI":"10.1007\/s00424-023-02877-x","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T18:01:38Z","timestamp":1700676098000},"page":"243-256","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age-dependent effects of the \u03b23 adrenoceptor agonist CL316,243 on human and rat detrusor muscle strips"],"prefix":"10.1007","volume":"476","author":[{"given":"Charlotte","family":"Petereit","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Porath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Rackow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karoline","family":"Kernig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3684-4179","authenticated-orcid":false,"given":"Oliver W.","family":"Hakenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3330-4898","authenticated-orcid":false,"given":"R\u00fcdiger","family":"K\u00f6hling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2812-2440","authenticated-orcid":false,"given":"Timo","family":"Kirschstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"2877_CR1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/nau.10052","volume":"21","author":"P Abrams","year":"2002","unstructured":"Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A (2002) The standardisation of terminology of lower urinary tract function: report from the Standardisation Subcommittee of the International Continence Society. Neurourol Urodyn 21:167\u2013178. https:\/\/doi.org\/10.1002\/nau.10052","journal-title":"Neurourol Urodyn"},{"issue":"4","key":"2877_CR2","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.urology.2007.01.059","volume":"69","author":"JK Badawi","year":"2007","unstructured":"Badawi JK, Seja T, Uecelehan H, Honeck P, Kwon ST, Bross S, Langbein S (2007) Relaxation of human detrusor muscle by selective beta-2 and beta-3 agonists and endogenous catecholamines. Urology 69(4):785\u2013790. https:\/\/doi.org\/10.1016\/j.urology.2007.01.059","journal-title":"Urology"},{"issue":"2","key":"2877_CR3","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/j.1365-201X.2005.01474.x","volume":"185","author":"JK Badawi","year":"2005","unstructured":"Badawi JK, Uecelehan H, Hatzinger M, Michel MS, Haferkamp A, Bross S (2005) Relaxant effects of beta-adrenergic agonists on porcine and human detrusor muscle. Acta Physiol Scand 185(2):151\u2013159. https:\/\/doi.org\/10.1111\/j.1365-201X.2005.01474.x","journal-title":"Acta Physiol Scand"},{"issue":"3","key":"2877_CR4","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/sj.bjp.0706048","volume":"144","author":"JG Baker","year":"2005","unstructured":"Baker JG (2005) The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol 144(3):317\u2013322. https:\/\/doi.org\/10.1038\/sj.bjp.0706048","journal-title":"Br J Pharmacol"},{"issue":"6","key":"2877_CR5","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1111\/j.1464-410X.2006.06564.x","volume":"98","author":"SM Biers","year":"2006","unstructured":"Biers SM, Reynard JM, Brading AF (2006) The effects of a new selective beta3-adrenoceptor agonist (GW427353) on spontaneous activity and detrusor relaxation in human bladder. BJU Int 98(6):1310\u20131314. https:\/\/doi.org\/10.1111\/j.1464-410X.2006.06564.x","journal-title":"BJU Int"},{"key":"2877_CR6","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1021\/jm00094a025","volume":"35","author":"JD Bloom","year":"1992","unstructured":"Bloom JD, Dutia MD, Johnson BD, Wissner A, Burns MG, Largis EE, Dolan JA, Claus TH (1992) Disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316,243). A potent beta-adrenergic agonist virtually specific for beta 3 receptors. A promising antidiabetic and antiobesity agent. J Med Chem 35:3081\u20133084. https:\/\/doi.org\/10.1021\/jm00094a025","journal-title":"J Med Chem"},{"issue":"7","key":"2877_CR7","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s00210-015-1128-z","volume":"388","author":"H Cernecka","year":"2015","unstructured":"Cernecka H, Kersten K, Maarsingh H, Elzinga CR, de Jong IJ, Korstanje C, Michel MC, Schmidt M (2015) \u03b23-Adrenoceptor-mediated relaxation of rat and human urinary bladder: roles of BKCa channels and Rho kinase. Naunyn Schmiedebergs Arch Pharmacol 388(7):749\u2013759. https:\/\/doi.org\/10.1007\/s00210-015-1128-z","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"11","key":"2877_CR8","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1016\/j.clinthera.2013.08.017","volume":"35","author":"MB Chancellor","year":"2013","unstructured":"Chancellor MB, Migliaccio-Walle K, Bramley TJ, Chaudhari SL, Corbell C, Globe D (2013) Long-term patterns of use and treatment failure with anticholinergic agents for overactive bladder. Clin Ther 35(11):1744\u20131751. https:\/\/doi.org\/10.1016\/j.clinthera.2013.08.017","journal-title":"Clin Ther"},{"issue":"1","key":"2877_CR9","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/nau.22505","volume":"33","author":"CR Chapple","year":"2014","unstructured":"Chapple CR, Cardozo L, Nitti VW, Siddiqui E, Michel MC (2014) Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability. Neurourol Urodyn 33(1):17\u201330. https:\/\/doi.org\/10.1002\/nau.22505","journal-title":"Neurourol Urodyn"},{"issue":"3","key":"2877_CR10","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1046\/j.1474-8673.2002.00258.x","volume":"22","author":"R Chess-Williams","year":"2002","unstructured":"Chess-Williams R (2002) Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional. Auton Autacoid Pharmacol 22(3):133\u2013145. https:\/\/doi.org\/10.1046\/j.1474-8673.2002.00258.x","journal-title":"Auton Autacoid Pharmacol"},{"issue":"5-6","key":"2877_CR11","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1046\/j.1365-2680.2001.00231.x","volume":"21","author":"R Chess-Williams","year":"2001","unstructured":"Chess-Williams R, Chapple CR, Yamanishi T, Yasuda K, Sellers DJ (2001) The minor population of M3-receptors mediate contraction of human detrusor muscle in vitro. J Auton Pharmacol 21(5-6):243\u2013248. https:\/\/doi.org\/10.1046\/j.1365-2680.2001.00231.x","journal-title":"J Auton Pharmacol"},{"key":"2877_CR12","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ejphar.2015.03.074","volume":"758","author":"G D` Agostino","year":"2015","unstructured":"D` Agostino G, Condino AM, Calvi P (2015) Involvement of \u03b23-adrenoceptors in the inhibitory control of cholinergic activity in human bladder: direct evidence by [(3)H]-acetylcholine release experiments in the isolated detrusor. Eur J Pharmacol 758:115\u2013122. https:\/\/doi.org\/10.1016\/j.ejphar.2015.03.074","journal-title":"Eur J Pharmacol"},{"key":"2877_CR13","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/nau.23990","volume":"38","author":"MG de Oliveira","year":"2019","unstructured":"de Oliveira MG, Alexandre EC, Bonilla-Becerra SM, Bertollotto GM, Oliveira Justo AF, M\u00f3nica FZ, Antunes E (2019) Autonomic dysregulation at multiple sites is implicated in age-associated underactive bladder in female mice. Neurourol Urodyn 38:1212\u20131221. https:\/\/doi.org\/10.1002\/nau.23990","journal-title":"Neurourol Urodyn"},{"key":"2877_CR14","first-page":"969","volume":"294","author":"IH Derweesh","year":"2000","unstructured":"Derweesh IH, Wheeler MA, Weiss RM (2000) Alterations in G-proteins and beta -adrenergic responsive adenylyl cyclase in rat urinary bladder during aging. J Pharmacol Exp Ther 294:969\u2013974","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"2877_CR15","first-page":"1000","volume":"269","author":"JA Dolan","year":"1994","unstructured":"Dolan JA, Muenkel HA, Burns MG, Pellegrino SM, Fraser CM, Pietri F, Strosberg AD, Largis EE, Dutia MD, Bloom JD, Bass AS, Tanikella TK, Cobuzzi A, Lai FM, Claus TH (1994) Beta-3 adrenoceptor selectivity of the dioxolane dicarboxylate phenethanolamines. J Pharmacol Exp Ther 269(3):1000\u20131006","journal-title":"J Pharmacol Exp Ther"},{"key":"2877_CR16","doi-asserted-by":"publisher","first-page":"29S","DOI":"10.1016\/j.amjmed.2005.12.014","volume":"119","author":"N Erdem","year":"2006","unstructured":"Erdem N, Chu FM (2006) Management of overactive bladder and urge urinary incontinence in the elderly patient. Am J Med 119:29S\u201336S. https:\/\/doi.org\/10.1016\/j.amjmed.2005.12.014","journal-title":"Am J Med"},{"issue":"1","key":"2877_CR17","doi-asserted-by":"publisher","first-page":"C131","DOI":"10.1152\/ajpcell.00488.2018","volume":"317","author":"Z Fong","year":"2019","unstructured":"Fong Z, Griffin CS, Hollywood MA, Thornbury KD, Sergeant GP (2019) \u03b23-Adrenoceptor agonists inhibit purinergic receptor-mediated contractions of the murine detrusor. Am J Physiol Cell Physiol 317(1):C131\u2013C142. https:\/\/doi.org\/10.1152\/ajpcell.00488.2018","journal-title":"Am J Physiol Cell Physiol"},{"key":"2877_CR18","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1007\/s00210-006-0077-y","volume":"373","author":"EP Frazier","year":"2006","unstructured":"Frazier EP, Schneider T, Michel MC (2006) Effects of gender, age and hypertension on beta-adrenergic receptor function in rat urinary bladder. Naunyn Schmiedebergs Arch Pharmacol 373:300\u2013309. https:\/\/doi.org\/10.1007\/s00210-006-0077-y","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"11","key":"2877_CR19","doi-asserted-by":"publisher","first-page":"F1447","DOI":"10.1152\/ajprenal.00436.2011","volume":"302","author":"CH Fry","year":"2012","unstructured":"Fry CH, Young JS, Jabr RI, McCarthy C, Ikeda Y, Kanai AJ (2012) Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists. Am J Physiol Renal Physiol 302(11):F1447\u2013F1454. https:\/\/doi.org\/10.1152\/ajprenal.00436.2011","journal-title":"Am J Physiol Renal Physiol"},{"issue":"2","key":"2877_CR20","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/S0022-5347(01)61994-3","volume":"161","author":"T Fujimura","year":"1999","unstructured":"Fujimura T, Tamura K, Tsutsumi T, Yamamoto T, Nakamura K, Koibuchi Y, Kobayashi M, Yamaguchi O (1999) Expression and possible functional role of the beta3-adrenoceptor in human and rat detrusor muscle. J Urol 161(2):680\u2013685","journal-title":"J Urol"},{"issue":"8","key":"2877_CR21","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1038\/sj.bjp.0701048","volume":"120","author":"SS Hegde","year":"1997","unstructured":"Hegde SS, Choppin A, Bonhaus D, Briaud S, Loeb M, Moy TM, Loury D, Eglen RM (1997) Functional role of M2 and M3 muscarinic receptors in the urinary bladder of rats in vitro and in vivo. Br J Pharmacol 120(8):1409\u20131418. https:\/\/doi.org\/10.1038\/sj.bjp.0701048","journal-title":"Br J Pharmacol"},{"issue":"3","key":"2877_CR22","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/sj.bjp.0702358","volume":"126","author":"Y Igawa","year":"1999","unstructured":"Igawa Y, Yamazaki Y, Takeda H, Hayakawa K, Akahane M, Ajisawa Y, Yoneyama T, Nishizawa O, Andersson KE (1999) Functional and molecular biological evidence for a possible beta3-adrenoceptor in the human detrusor muscle. Br J Pharmacol 126(3):819\u2013825. https:\/\/doi.org\/10.1038\/sj.bjp.0702358","journal-title":"Br J Pharmacol"},{"issue":"1","key":"2877_CR23","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1097\/00005392-200101000-00071","volume":"165","author":"Y Igawa","year":"2001","unstructured":"Igawa Y, Yamazaki Y, Takeda H, Kaidoh K, Akahane M, Ajisawa Y, Yoneyama T, Nishizawa O, Andersson KE (2001) Relaxant effects of isoproterenol and selective beta3-adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders. J Urol 165(1):240\u2013244. https:\/\/doi.org\/10.1097\/00005392-200101000-00071","journal-title":"J Urol"},{"key":"2877_CR24","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.eururo.2006.09.019","volume":"50","author":"DE Irwin","year":"2006","unstructured":"Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, Coyne K, Kelleher C, Hampel C, Artibani W, Abrams P (2006) Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 50:1306\u20131314. https:\/\/doi.org\/10.1016\/j.eururo.2006.09.019","journal-title":"Eur Urol"},{"issue":"1","key":"2877_CR25","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/aps.2013.126","volume":"35","author":"T Kirschstein","year":"2014","unstructured":"Kirschstein T, Protzel C, Porath K, Sellmann T, K\u00f6hling R, Hakenberg OW (2014) Age-dependent contribution of Rho kinase in carbachol-induced contraction of human detrusor smooth muscle in vitro. Acta Pharmacol Sin 35(1):74\u201381. https:\/\/doi.org\/10.1038\/aps.2013.126","journal-title":"Acta Pharmacol Sin"},{"issue":"8","key":"2877_CR26","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/aps.2009.98","volume":"30","author":"T Kirschstein","year":"2009","unstructured":"Kirschstein T, Rehberg M, Bajorat R, Tokay T, Porath K, K\u00f6hling R (2009) High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle. Acta Pharmacol Sin 30(8):1123\u20131131. https:\/\/doi.org\/10.1038\/aps.2009.98","journal-title":"Acta Pharmacol Sin"},{"key":"2877_CR27","first-page":"1511","volume":"116","author":"G Li","year":"2003","unstructured":"Li G, Li K, Li Z, Wang P (2003) Age-dependent changes in beta-adrenoceptor function in human detrusors and possible mechanisms. Chin Med J (Engl) 116:1511\u20131514","journal-title":"Chin Med J (Engl)"},{"key":"2877_CR28","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00441-010-1053-x","volume":"342","author":"BJ Limberg","year":"2010","unstructured":"Limberg BJ, Andersson KE, Kullmann FA, Burmer G, de Groat WC, Rosenbaum JS (2010) \u03b2-Adrenergic receptor subtype expression in myocyte and non-myocyte cells in human female bladder. Cell Tissue Res 342:295\u2013306. https:\/\/doi.org\/10.1007\/s00441-010-1053-x","journal-title":"Cell Tissue Res"},{"issue":"4","key":"2877_CR29","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1111\/j.1476-5381.1995.tb15065.x","volume":"116","author":"PA Longhurst","year":"1995","unstructured":"Longhurst PA, Leggett RE, Briscoe JA (1995) Characterization of the functional muscarinic receptors in the rat urinary bladder. Br J Pharmacol 116(4):2279\u20132285. https:\/\/doi.org\/10.1111\/j.1476-5381.1995.tb15065.x","journal-title":"Br J Pharmacol"},{"issue":"7","key":"2877_CR30","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1038\/sj.bjp.0702709","volume":"127","author":"PA Longhurst","year":"1999","unstructured":"Longhurst PA, Levendusky M (1999) Pharmacological characterization of beta-adrenoceptors mediating relaxation of the rat urinary bladder in vitro. Br J Pharmacol 127(7):1744\u20131750. https:\/\/doi.org\/10.1038\/sj.bjp.0702709","journal-title":"Br J Pharmacol"},{"issue":"5","key":"2877_CR31","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1007\/s12325-020-01318-w","volume":"37","author":"G Lozano-Ortega","year":"2020","unstructured":"Lozano-Ortega G, Ng DB, Szabo SM, Deighton AM, Riveros B, Guttschow A, Gooch KL, Gomes CM (2020) Management of patients with overactive bladder in Brazil: a retrospective observational study using data from the Brazilian Public Health System. Adv Ther 37(5):2344\u20132355. https:\/\/doi.org\/10.1007\/s12325-020-01318-w","journal-title":"Adv Ther"},{"key":"2877_CR32","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3389\/fphys.2018.00753","volume":"9","author":"F Mader","year":"2018","unstructured":"Mader F, M\u00fcller S, Krause L, Springer A, Kernig K, Protzel C, Porath K, Rackow S, Wittstock T, Frank M, Hakenberg OW, K\u00f6hling R, Kirschstein T (2018) Hyperpolarization-activated cyclic nucleotide-gated non-selective (HCN) ion channels regulate human and murine urinary bladder contractility. Front Physiol 9:753. https:\/\/doi.org\/10.3389\/fphys.2018.00753","journal-title":"Front Physiol"},{"key":"2877_CR33","doi-asserted-by":"publisher","first-page":"CD005429","DOI":"10.1002\/14651858.CD005429.pub2","volume":"1","author":"P Madhuvrata","year":"2012","unstructured":"Madhuvrata P, Cody JD, Ellis G, Herbison GP, Hay-Smith EJC (2012) Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev 1:CD005429. https:\/\/doi.org\/10.1002\/14651858.CD005429.pub2","journal-title":"Cochrane Database Syst Rev"},{"issue":"2","key":"2877_CR34","doi-asserted-by":"publisher","first-page":"F257","DOI":"10.1152\/ajprenal.00048.2020","volume":"319","author":"J Malysz","year":"2020","unstructured":"Malysz J, Petkov GV (2020) Urinary bladder smooth muscle ion channels: expression, function, and regulation in health and disease. Am J Physiol Renal Physiol 319(2):F257\u2013F283. https:\/\/doi.org\/10.1152\/ajprenal.00048.2020","journal-title":"Am J Physiol Renal Physiol"},{"issue":"1","key":"2877_CR35","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1124\/jpet.102.044701","volume":"305","author":"M Matsui","year":"2003","unstructured":"Matsui M, Griffin MT, Shehnaz D, Taketo MM, Ehlert FJ (2003) Increased relaxant action of forskolin and isoproterenol against muscarinic agonist-induced contractions in smooth muscle from M2 receptor knockout mice. J Pharmacol Exp Ther 305(1):106\u2013113. https:\/\/doi.org\/10.1124\/jpet.102.044701","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"2877_CR36","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12894-022-00989-7","volume":"22","author":"H Nakagomi","year":"2022","unstructured":"Nakagomi H, Mitsui T, Shimura H, Ihara T, Kira S, Sawada N, Takeda M (2022) Mirabegron for overactive bladder in frail patients 80 years or over (HOKUTO study). BMC Urol 22(1):40. https:\/\/doi.org\/10.1186\/s12894-022-00989-7","journal-title":"BMC Urol"},{"key":"2877_CR37","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00210-006-0104-z","volume":"374","author":"N Niclau\u00df","year":"2006","unstructured":"Niclau\u00df N, Michel-Reher MB, Alewijnse AE, Michel MC (2006) Comparison of three radioligands for the labelling of human beta-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol 374:99\u2013105. https:\/\/doi.org\/10.1007\/s00210-006-0104-z","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"2877_CR38","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1016\/S0022-5347(01)67508-6","volume":"153","author":"T Nishimoto","year":"1995","unstructured":"Nishimoto T, Latifpour J, Wheeler MA, Yoshida M, Weiss RM (1995) Age-dependent alterations in beta-adrenergic responsiveness of rat detrusor smooth muscle. J Urol 153:1701\u20131705. https:\/\/doi.org\/10.1016\/S0022-5347(01)67508-6","journal-title":"J Urol"},{"key":"2877_CR39","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1097\/01.ju.0000067621.62736.7c","volume":"170","author":"M Nomiya","year":"2003","unstructured":"Nomiya M, Yamaguchi O (2003) A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders. J Urol 170:649\u2013653. https:\/\/doi.org\/10.1097\/01.ju.0000067621.62736.7c","journal-title":"J Urol"},{"issue":"3","key":"2877_CR40","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/luts.12007","volume":"5","author":"A Otsuka","year":"2013","unstructured":"Otsuka A, Kawasaki H, Matsumoto R, Shinbo H, Kurita Y, Iwashita T, Ozono S (2013) Expression of \u03b2-adrenoceptor subtypes in urothelium, interstitial cells and detrusor of the human urinary bladder. Low Urin Tract Symptoms 5(3):173\u2013180. https:\/\/doi.org\/10.1111\/luts.12007","journal-title":"Low Urin Tract Symptoms"},{"issue":"4","key":"2877_CR41","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00210-009-0393-0","volume":"379","author":"W Pradidarcheep","year":"2009","unstructured":"Pradidarcheep W, Stallen J, Labruy\u00e8re WT, Dabhoiwala NF, Michel MC, Lamers WH (2009) Lack of specificity of commercially available antisera against muscarinergic and adrenergic receptors. Naunyn Schmiedebergs Arch Pharmacol 379(4):397\u2013402. https:\/\/doi.org\/10.1007\/s00210-009-0393-0","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"2877_CR42","doi-asserted-by":"publisher","first-page":"799","DOI":"10.2147\/IJWH.S369588","volume":"15","author":"D Robinson","year":"2023","unstructured":"Robinson D, O'Kane M, Cardozo L (2023) Adherence to overactive bladder syndrome treatments recent developments and future perspectives. Int J Womens Health 15:799\u2013811. https:\/\/doi.org\/10.2147\/IJWH.S369588","journal-title":"Int J Womens Health"},{"key":"2877_CR43","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.phrs.2013.12.006","volume":"80","author":"C Rouget","year":"2014","unstructured":"Rouget C, Rekik M, Camparo P, Botto H, Rischmann P, Lluel P, Palea S, Westfall TD (2014) Modulation of nerve-evoked contractions by \u03b23-adrenoceptor agonism in human and rat isolated urinary bladder. Pharmacol Res 80:14\u201320. https:\/\/doi.org\/10.1016\/j.phrs.2013.12.006","journal-title":"Pharmacol Res"},{"issue":"6","key":"2877_CR44","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1016\/S0022-5347(01)63305-6","volume":"159","author":"H Seguchi","year":"1998","unstructured":"Seguchi H, Nishimura J, Zhou Y, Niiro N, Kumazawa J, Kanaide H (1998) Expression of beta3-adrenoceptors in rat detrusor smooth muscle. J Urol 159(6):2197\u20132201. https:\/\/doi.org\/10.1016\/S0022-5347(01)63305-6","journal-title":"J Urol"},{"issue":"5","key":"2877_CR45","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1111\/j.1742-1241.2010.02626.x","volume":"65","author":"CC Sexton","year":"2011","unstructured":"Sexton CC, Notte SM, Maroulis C, Dmochowski RR, Cardozo L, Subramanian D, Coyne KS (2011) Persistence and adherence in the treatment of overactive bladder syndrome with anticholinergic therapy: a systematic review of the literature. Int J Clin Pract 65(5):567\u2013585. https:\/\/doi.org\/10.1111\/j.1742-1241.2010.02626.x","journal-title":"Int J Clin Pract"},{"issue":"2","key":"2877_CR46","doi-asserted-by":"publisher","first-page":"F388","DOI":"10.1152\/ajprenal.00392.2016","volume":"313","author":"I Silva","year":"2017","unstructured":"Silva I, Costa AF, Moreira S, Ferreirinha F, Magalh\u00e3es-Cardoso MT, Calejo I, Silva-Ramos M, Correia-de-S\u00e1 P (2017) Inhibition of cholinergic neurotransmission by \u03b23-adrenoceptors depends on adenosine release and A1-receptor activation in human and rat urinary bladders. Am J Physiol Renal Physiol 313(2):F388\u2013F403. https:\/\/doi.org\/10.1152\/ajprenal.00392.2016","journal-title":"Am J Physiol Renal Physiol"},{"key":"2877_CR47","doi-asserted-by":"publisher","first-page":"102689","DOI":"10.1016\/j.autneu.2020.102689","volume":"227","author":"J Stenqvist","year":"2020","unstructured":"Stenqvist J, Aronsson P, Carlsson T, Winder M, Tobin G (2020) In vivo paracrine effects of ATP-induced urothelial acetylcholine in the rat urinary bladder. Auton Neurosci. 227:102689. https:\/\/doi.org\/10.1016\/j.autneu.2020.102689","journal-title":"Auton Neurosci."},{"issue":"1-3","key":"2877_CR48","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ejphar.2012.11.060","volume":"699","author":"J Sval\u00f8","year":"2013","unstructured":"Sval\u00f8 J, Nordling J, Bouchelouche K, Andersson KE, Korstanje C, Bouchelouche P (2013) The novel \u03b23-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity. Eur J Pharmacol 699(1-3):101\u2013105. https:\/\/doi.org\/10.1016\/j.ejphar.2012.11.060","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"2877_CR49","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1124\/jpet.106.115840","volume":"321","author":"T Takasu","year":"2007","unstructured":"Takasu T, Ukai M, Sato S, Matsui T, Nagase I, Maruyama T, Sasamata M, Miyata K, Uchida H, Yamaguchi O (2007) Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther 321(2):642\u2013647. https:\/\/doi.org\/10.1124\/jpet.106.115840","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"2877_CR50","first-page":"1367","volume":"288","author":"M Takeda","year":"1999","unstructured":"Takeda M, Obara K, Mizusawa T, Tomita Y, Arai K, Tsutsui T, Hatano A, Takahashi K, Nomura S (1999) Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods. J Pharmacol Exp Ther 288(3):1367\u20131373","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"2877_CR51","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1590\/s1677-55382009000100012","volume":"35","author":"P Tyagi","year":"2009","unstructured":"Tyagi P, Thomas CA, Yoshimura N, Chancellor MB (2009) Investigations into the presence of functional Beta1, Beta2 and Beta3-adrenoceptors in urothelium and detrusor of human bladder. Int Braz J Urol 35(1):76\u201383. https:\/\/doi.org\/10.1590\/s1677-55382009000100012","journal-title":"Int Braz J Urol"},{"issue":"6220","key":"2877_CR52","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","volume":"347","author":"M Uhl\u00e9n","year":"2015","unstructured":"Uhl\u00e9n M, Fagerberg L, Hallstr\u00f6m BM, Lindskog C, Oksvold P, Mardinoglu A et al (2015) Proteomics. Tissue-based map of the human proteome. Science 347(6220):1260419. https:\/\/doi.org\/10.1126\/science.1260419","journal-title":"Science"},{"issue":"1","key":"2877_CR53","first-page":"277","volume":"254","author":"MA Wheeler","year":"1990","unstructured":"Wheeler MA, Pontari M, Nishimoto T, Weiss RM (1990) Changes in lipid composition and isoproterenol- and ethanol-stimulated adenylate cyclase activity in aging Fischer rat bladders. J Pharmacol Exp Ther 254(1):277\u2013283","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"2877_CR54","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/S0022-5347(05)65936-8","volume":"166","author":"M Woods","year":"2001","unstructured":"Woods M, Carson N, Norton NW, Sheldon JH, Argentieri TM (2001) Efficacy of the beta3-adrenergic receptor agonist CL-316243 on experimental bladder hyperreflexia and detrusor instability in the rat. J Urol 166(3):1142\u20131147","journal-title":"J Urol"},{"issue":"3-4","key":"2877_CR55","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.ceca.2005.06.018","volume":"38","author":"S Wray","year":"2005","unstructured":"Wray S, Burdyga T, Noble K (2005) Calcium signalling in smooth muscle. Cell Calcium 38(3-4):397\u2013407. https:\/\/doi.org\/10.1016\/j.ceca.2005.06.018","journal-title":"Cell Calcium"},{"issue":"1","key":"2877_CR56","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1124\/jpet.108.142562","volume":"328","author":"M Wuest","year":"2009","unstructured":"Wuest M, Eichhorn B, Grimm MO, Wirth MP, Ravens U, Kaumann AJ (2009) Catecholamines relax detrusor through beta 2-adrenoceptors in mouse and beta 3-adrenoceptors in man. J Pharmacol Exp Ther 328(1):213\u2013222. https:\/\/doi.org\/10.1124\/jpet.108.142562","journal-title":"J Pharmacol Exp Ther"},{"issue":"7","key":"2877_CR57","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1002\/nau.20231","volume":"25","author":"T Yamanishi","year":"2006","unstructured":"Yamanishi T, Yasuda K, Kitahara S, Nakai H, Yoshida K, Iizuka H (2006) Effects of 138-355, a beta3-adrenoceptor selective agonist, on relaxation of the human detrusor muscle in vitro. Neurourol Urodyn 25(7):815\u2013819. https:\/\/doi.org\/10.1002\/nau.20231","journal-title":"Neurourol Urodyn"},{"issue":"3","key":"2877_CR58","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/sj.bjp.0701870","volume":"124","author":"Y Yamazaki","year":"1998","unstructured":"Yamazaki Y, Takeda H, Akahane M, Igawa Y, Nishizawa O, Ajisawa Y (1998) Species differences in the distribution of beta-adrenoceptor subtypes in bladder smooth muscle. Br J Pharmacol 124(3):593\u2013599. https:\/\/doi.org\/10.1038\/sj.bjp.0701870","journal-title":"Br J Pharmacol"},{"issue":"3","key":"2877_CR59","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1620\/tjem.192.181","volume":"192","author":"T Yanagisawa","year":"2000","unstructured":"Yanagisawa T, Sato T, Yamada H, Sukegawa J, Nunoki K (2000) Selectivity and potency of agonists for the three subtypes of cloned human beta-adrenoceptors expressed in Chinese hamster ovary cells. Tohoku J Exp Med 192(3):181\u2013193. https:\/\/doi.org\/10.1620\/tjem.192.181","journal-title":"Tohoku J Exp Med"}],"container-title":["Pfl\u00fcgers Archiv - European Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-023-02877-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00424-023-02877-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-023-02877-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T04:54:32Z","timestamp":1705467272000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00424-023-02877-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,22]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["2877"],"URL":"https:\/\/doi.org\/10.1007\/s00424-023-02877-x","relation":{},"ISSN":["0031-6768","1432-2013"],"issn-type":[{"type":"print","value":"0031-6768"},{"type":"electronic","value":"1432-2013"}],"subject":[],"published":{"date-parts":[[2023,11,22]]},"assertion":[{"value":"1 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All in vitro experiments with human material were approved by the local ethics committee (University Medicine of Rostock), and informed consent to participate in this study was obtained from each patient. All animal experiments were performed according to the international and national guidelines for the use of experimental animals. All experimenters involved in anaesthesia and killing have been accredited (certificate from the Federation of European Laboratory Animal Science Associations) and approved by the animal committee (Landesamt f\u00fcr Landwirtschaft, Lebensmittelsicherheit und Fischerei Mecklenburg-Vorpommern, approval no. 7221.3-1.2-007\/10).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All authors have seen and approved the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}