{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:55:41Z","timestamp":1777481741505,"version":"3.51.4"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015502","name":"Dialysis Clinics","doi-asserted-by":"publisher","award":["C-4095 and C-4192"],"award-info":[{"award-number":["C-4095 and C-4192"]}],"id":[{"id":"10.13039\/100015502","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Purinergic Signalling"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We have previously reported that adenine at high doses interferes with the vasopressin signaling pathway, causes massive diuresis and volume depletion, and ultimately leads to renal failure. In the present study, we examined the effects of adenine on renal salt and water handling in a time course and dose\u2013response study in rats housed in metabolic cages and fed control or adenine-containing diet at 1500, 2000, 2500\u00a0mg\/kg and euthanized after 1, 3, and 7\u00a0weeks. Adenine at 2000 and 2500\u00a0mg\/kg caused early and significant polyuria, polydipsia, and decreased urine osmolality in a dose-dependent manner without significantly affecting food intake, blood volume, blood electrolyte levels, or acid\u2013base composition. The impaired water balance resulted from the downregulation of apical water channel AQP2 in the outer and inner medulla but not in the cortex. Adenine did not alter electrolytes (Na\n                    <jats:sup>+<\/jats:sup>\n                    , K\n                    <jats:sup>+<\/jats:sup>\n                    , Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) excretion at these doses for up to 3\u00a0weeks. However, a slight but significant increase in salt excretion was observed in adenine-fed rats for 7\u00a0weeks, which correlates with a significant downregulation of NKCC2, mostly in rats fed 2500\u00a0mg\/kg adenine. Adenine-fed rats exhibited a substantial resistance to vasopressin in response to water deprivation or vasopressin treatment. Lastly, 2500\u00a0mg\/kg adenine prevented the development of hyponatremia in a rat experimental model of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In conclusion, adenine acts as an aquaretic agent in the kidney at lower doses and during a short feeding period. It can be used as a vasopressin antagonist in conditions associated with hyponatremia.\n                  <\/jats:p>","DOI":"10.1007\/s11302-025-10105-7","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T07:43:05Z","timestamp":1754984585000},"page":"1261-1275","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adenine at lower doses acts in the kidney as an aquaretic agent and prevents hyponatremia"],"prefix":"10.1007","volume":"21","author":[{"given":"Alaa","family":"Alghamdi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charuhas V.","family":"Thakar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassane","family":"Amlal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"10105_CR1","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1248\/bpb.32.1204","volume":"32","author":"K Ienaga","year":"2009","unstructured":"Ienaga K, Mikami H, Yokozawa T (2009) First indications demonstrating the preventive effects of NZ-419, a novel intrinsic antioxidant, on the initiation and\/or progression of chronic renal failure in rats. Biol Pharm Bull 32:1204\u20131208","journal-title":"Biol Pharm Bull"},{"key":"10105_CR2","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.etp.2010.02.002","volume":"63","author":"M Shuvy","year":"2011","unstructured":"Shuvy M, Nyska A, Beeri R, Abedat S, Gal-Moscovici A, Rajamannan NM, Lotan C (2011) Histopathology and apoptosis in an animal model of reversible renal injury. Exp Toxicol Pathol 63:303\u2013306","journal-title":"Exp Toxicol Pathol"},{"key":"10105_CR3","doi-asserted-by":"publisher","first-page":"519","DOI":"10.3177\/jnsv.28.519","volume":"28","author":"T Yokozawa","year":"1982","unstructured":"Yokozawa T, Oura H, Okada T (1982) Metabolic effects of dietary purine in rats. J Nutr Sci Vitaminol (Tokyo) 28:519\u2013526","journal-title":"J Nutr Sci Vitaminol (Tokyo)"},{"key":"10105_CR4","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1159\/000183992","volume":"44","author":"T Yokozawa","year":"1986","unstructured":"Yokozawa T, Zheng PD, Oura H, Koizumi F (1986) Animal model of adenine-induced chronic renal failure in rats. Nephron 44:230\u2013234","journal-title":"Nephron"},{"key":"10105_CR5","doi-asserted-by":"publisher","first-page":"499","DOI":"10.7326\/0003-4819-143-7-200510040-00009","volume":"143","author":"HK Choi","year":"2005","unstructured":"Choi HK, Mount DB, Reginato AM (2005) Pathogenesis of gout. Ann Intern Med 143:499\u2013516","journal-title":"Ann Intern Med"},{"key":"10105_CR6","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1161\/01.RES.65.3.531","volume":"65","author":"SB Coade","year":"1989","unstructured":"Coade SB, Pearson JD (1989) Metabolism of adenine nucleotides in human blood. Circ Res 65:531\u2013537","journal-title":"Circ Res"},{"key":"10105_CR7","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1124\/mol.104.006601","volume":"67","author":"S Gorzalka","year":"2005","unstructured":"Gorzalka S, Vittori S, Volpini R, Cristalli G, von K\u00fcgelgen I, M\u00fcller CE (2005) Evidence for the functional expression and pharmacological characterization of adenine receptors in native cells and tissues. Mol Pharmacol 67:955\u2013964","journal-title":"Mol Pharmacol"},{"key":"10105_CR8","doi-asserted-by":"publisher","first-page":"265","DOI":"10.2147\/VHRM.S4265","volume":"5","author":"J George","year":"2009","unstructured":"George J, Struthers AD (2009) Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag 5:265\u2013272","journal-title":"Vasc Health Risk Manag"},{"key":"10105_CR9","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/0003-9861(57)90088-7","volume":"70","author":"JB Wyngaarden","year":"1957","unstructured":"Wyngaarden JB, Dunn JT (1957) 8-hydroxyadenine as the intermediate in the oxidation of adenine to 2,8-dihydroxyadenine by xanthine oxidase. Arch Biochem Biophys 70:150\u2013156","journal-title":"Arch Biochem Biophys"},{"key":"10105_CR10","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1046\/j.1537-2995.1977.17477216867.x","volume":"17","author":"CC Peck","year":"1977","unstructured":"Peck CC, Bailey FJ, Moore GL (1977) Enhanced solubility of 2,8 dihydroxyadenine (DOA) in human urine. Transfusion 17:383\u2013390","journal-title":"Transfusion"},{"key":"10105_CR11","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0009-8981(86)90129-4","volume":"160","author":"HA Simmonds","year":"1986","unstructured":"Simmonds HA (1986) 2,8-Dihydroxyadenine lithiasis. Clin Chim Acta 160:103\u2013108","journal-title":"Clin Chim Acta"},{"issue":"4","key":"10105_CR12","doi-asserted-by":"publisher","first-page":"F743","DOI":"10.1152\/ajprenal.00142.2018","volume":"316","author":"IF Dos Santos","year":"2019","unstructured":"Dos Santos IF, Sheriff S, Amlal S, Ahmed RP, Thakar CV, Amlal H (2019) Adenine acts in the kidney as a signaling factor and causes salt- and water-losing nephropathy: Early mechanism of adenine-induced renal injury. Am J Physiol Renal Physiol 316(4):F743\u2013F757","journal-title":"Am J Physiol Renal Physiol"},{"key":"10105_CR13","doi-asserted-by":"publisher","first-page":"8573","DOI":"10.1073\/pnas.122016499","volume":"99","author":"E Bender","year":"2002","unstructured":"Bender E, Buist A, Jurzak M, Langlois X, Baggerman G, Verhasselt P, Ercken M, Guo HQ, Wintmolders C, Van den Wyngaert I, Van Oers I, Schoofs L, Luyten W (2002) Characterization of an orphan G protein coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc Natl Acad Sci USA 99:8573\u20138578","journal-title":"Proc Natl Acad Sci USA"},{"key":"10105_CR14","doi-asserted-by":"publisher","first-page":"F1298","DOI":"10.1152\/ajprenal.00254.2013","volume":"305","author":"BK Kishore","year":"2013","unstructured":"Kishore BK, Zhang Y, Gevorgyan H, Kohan DE, Schiedel AC, M\u00fcller CE, Peti-Peterdi J (2013) Cellular localization of adenine receptors in the rat kidney and their functional significance in the inner medullary collecting duct. Am J Physiol Renal Physiol 305:F1298\u2013F1305","journal-title":"Am J Physiol Renal Physiol"},{"key":"10105_CR15","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s11302-013-9360-9","volume":"9","author":"D Thimm","year":"2013","unstructured":"Thimm D, Knospe M, Abdelrahaman A, Moutinho M, Alsdorf BB, von K\u00fcgelgen I, Schiedel AC, M\u00fcller CE (2013) Characterization of new G protein-coupled adenine receptors in mouse and hamster. Purinergic Signal 9:415\u2013426","journal-title":"Purinergic Signal"},{"key":"10105_CR16","doi-asserted-by":"publisher","first-page":"F513","DOI":"10.1152\/ajprenal.2001.280.3.F513","volume":"280","author":"H Amlal","year":"2001","unstructured":"Amlal H, Chen Q, Habo K, Wang Z, Soleimani M (2001) Fasting downregulates renal water channel AQP2 and causes polyuria. Am J Physiol Renal Physiol 280:F513\u2013F523","journal-title":"Am J Physiol Renal Physiol"},{"key":"10105_CR17","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1046\/j.1523-1755.2003.00110.x","volume":"64","author":"H Amlal","year":"2003","unstructured":"Amlal H, Wilke C (2003) Resistance of mTAL Na-dependent transporters and collecting duct aquaporins to dehydration in 7-month-old rats. Kidney Int 64:544\u2013554","journal-title":"Kidney Int"},{"key":"10105_CR18","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1111\/j.1523-1755.2005.00071.x","volume":"67","author":"C Wilke","year":"2005","unstructured":"Wilke C, Sheriff S, Soleimani M, Amlal H (2005) Vasopressin-independent regulation of collecting duct aquaporin-2 in food deprivation. Kidney Int 67:201\u2013216","journal-title":"Kidney Int"},{"key":"10105_CR19","first-page":"E540","volume":"247","author":"JG Verbalis","year":"1984","unstructured":"Verbalis JG (1984) An experimental model of syndrome of inappropriate antidiuretic hormone secretion in the rat. Am J Physiol 247:E540-553","journal-title":"Am J Physiol"},{"issue":"43","key":"10105_CR20","doi-asserted-by":"publisher","first-page":"F1161","DOI":"10.1152\/ajprenal.1998.274.6.F1161","volume":"274","author":"CA Ecelbarger","year":"1998","unstructured":"Ecelbarger CA, Chou C-L, Lee AJ, DiGiovanni SR, Verbalis JG, Knepper MA (1998) Escape from vasopressin-induced antidiuresis: role of vasopressin resistance of the collecting duct. Am J Physiol Renal Physiol 274(43):F1161\u2013F1166","journal-title":"Am J Physiol Renal Physiol"},{"key":"10105_CR21","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1001\/jama.291.16.1963","volume":"291","author":"M Gheorghiade","year":"2004","unstructured":"Gheorghiade M, Gattis WA, O\u2019Connor CM et al (2004) Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 291:1963\u20131971","journal-title":"JAMA"},{"key":"10105_CR22","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1046\/j.1523-1755.2001.00965.x","volume":"60","author":"T Saito","year":"2001","unstructured":"Saito T, Higashiyama M, Nagasaka S, Sasaki S, Saito T, Ishikawa SE (2001) Role of aquaporin2 gene expression in hyponatremic rats with chronic vasopressin-induced antidiuresis. Kidney Int 60:1266\u20131276","journal-title":"Kidney Int"},{"issue":"1","key":"10105_CR23","doi-asserted-by":"publisher","first-page":"F49","DOI":"10.1152\/ajprenal.00390.2005","volume":"291","author":"S Tiwari","year":"2006","unstructured":"Tiwari S, Packer RK, Hu X, Sugimura Y, Verbalis JG, Ecelbarger CA (2006) Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape. Am J Physiol Renal Physiol 291(1):F49-57","journal-title":"Am J Physiol Renal Physiol"},{"key":"10105_CR24","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.vascn.2013.05.006","volume":"68","author":"V Diwan","year":"2013","unstructured":"Diwan V, Mistry A, Gobe G, Brown L (2013) Adenine-induced chronic kidney and cardiovascular damage in rats. J Pharmacol Toxically Methods 68:197\u2013207","journal-title":"J Pharmacol Toxically Methods"},{"key":"10105_CR25","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1111\/apha.12452","volume":"213","author":"D Thimm","year":"2015","unstructured":"Thimm D, Schiedel AC, Peti-Peterdi J, Kishore BK, M\u00fcller CE (2015) The nucleobase adenine as a signalling molecule in the kidney. Acta Physiol (Oxf) 213:808\u2013818","journal-title":"Acta Physiol (Oxf)"},{"key":"10105_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/0886022X.2024.2336128","volume":"46","author":"Q Yang","year":"2024","unstructured":"Yang Q, Su Songya, Luo N, Cao G (2024) Adenine-induced animal model of chronic kidney disease: current applications and future perspectives. Ren Fail 46:1\u201320","journal-title":"Ren Fail"},{"key":"10105_CR27","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1124\/mol.107.037069","volume":"73","author":"I Von K\u00fcgelgen","year":"2008","unstructured":"Von K\u00fcgelgen I, Schiedel AC, Hoffmann K, Alsdorf BB, Abdelrahman A, M\u00fcller CE (2008) Cloning and functional expression of a novel Gi protein-coupled receptor for adenine from mouse brain. Mol Pharmacol 73:469\u2013477","journal-title":"Mol Pharmacol"},{"key":"10105_CR28","doi-asserted-by":"publisher","first-page":"164","DOI":"10.7326\/0003-4819-102-2-164","volume":"102","author":"RJ Anderson","year":"1985","unstructured":"Anderson RJ, Chung H, Kluge R, Schrier RW (1985) Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med 102:164\u2013168","journal-title":"Ann Intern Med"},{"key":"10105_CR29","unstructured":"Bichet DG, Kluge R, Howard RL, Schrier RW (1992) Hyponatremic states. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology. Raven, New York, NY, pp 1727\u20131751"},{"key":"10105_CR30","first-page":"163","volume":"34","author":"MV DeVita","year":"1990","unstructured":"DeVita MV, Gardenswartz MH, Konecky A, Zabetakis EM (1990) Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol 34:163\u2013166","journal-title":"Clin Nephrol"},{"key":"10105_CR31","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/S0140-6736(81)90261-0","volume":"2","author":"CT Flear","year":"1981","unstructured":"Flear CT, Gill GV, Burn J (1981) Hyponatremia: mechanisms and management. Lancet 2:26\u201331","journal-title":"Lancet"},{"key":"10105_CR32","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/j.1939-165x.2012.00488.x","volume":"41","author":"MJ Radin","year":"2012","unstructured":"Radin MJ, Yu MJ, Stoedkilde L, Miller RL, Hoffert JD, Frokiaer J, Pisitkun T, Knepper MA (2012) Aquaporin-2 regulation in health and disease. Vet Clin Pathol 41:455\u2013470","journal-title":"Vet Clin Pathol"},{"issue":"8","key":"10105_CR33","first-page":"625","volume":"6","author":"BJ Kinzie","year":"1987","unstructured":"Kinzie BJ (1987) Management of the syndrome of inappropriate secretion of antidiuretic hormone. Clin Pharrnacol 6(8):625\u2013633","journal-title":"Clin Pharrnacol"},{"key":"10105_CR34","doi-asserted-by":"publisher","first-page":"5450","DOI":"10.1073\/pnas.94.10.5450","volume":"94","author":"S Nielsen","year":"1997","unstructured":"Nielsen S, Terris J, Andersen D, Ecelbarger C, Frokiaer J, Jonassen T, Marples D, Knepper MA, Petersen JS (1997) Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct. Proc Natl Acad Sci U S A 94:5450\u20135455","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10105_CR35","first-page":"977","volume":"5","author":"SA Doggrell","year":"2004","unstructured":"Doggrell SA (2004) Tolvaptan (Otsuka). Curr Opin Investig Drugs 5:977\u2013983","journal-title":"Curr Opin Investig Drugs"},{"key":"10105_CR36","doi-asserted-by":"publisher","first-page":"F273","DOI":"10.1152\/ajprenal.00195.2005","volume":"290","author":"LC Costello-Boerrigter","year":"2006","unstructured":"Costello-Boerrigter LC, Smith WB, Boerrigter G et al (2006) Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Renal Physiol 290:F273\u2013F278","journal-title":"Am J Physiol Renal Physiol"},{"key":"10105_CR37","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/j.amjcard.2005.10.050","volume":"97","author":"M Gheorghiade","year":"2006","unstructured":"Gheorghiade M, Gottlieb SS, Udelson JE, Konstam MA, Czerwiec F, Ouyang J, Orlandi C (2006) Vasopressin V2 receptor blockade with tolvaptan versus fluid restriction in the treatment of hyponatremia. Am J Cardiol 97:1064\u20131067","journal-title":"Am J Cardiol"},{"key":"10105_CR38","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.1161\/01.CIR.0000070422.41439.04","volume":"107","author":"G Mihai","year":"2003","unstructured":"Mihai G, Niazi I, Ouyang J, Czerwiec F, Kambayashi J-I, Zampino M, Orlandi C (2003) Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 107:2690\u20132696","journal-title":"Circulation"},{"issue":"20","key":"10105_CR39","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1056\/NEJMoa065181","volume":"355","author":"RW Schrier","year":"2006","unstructured":"Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, Orlandi C (2006) Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 355(20):2099\u20132112","journal-title":"N Engl J Med"},{"key":"10105_CR40","first-page":"F926","volume":"269","author":"N Fujita","year":"1995","unstructured":"Fujita N, Ishikawa S, Sasaki S, Fujisawa G, Fushimi K, Marumo F, Saito T (1995) Role of water channel AQPCD in water retention in SIADH and cirrhotic rats. Am J Physiol 269:F926-931","journal-title":"Am J Physiol"},{"issue":"3","key":"10105_CR41","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1111\/j.1523-1755.2004.00843.x","volume":"66","author":"FA Belibi","year":"2004","unstructured":"Belibi FA, Reif G, Wallace DP, Yamaguchi T, Olsen L, Li H, Helmkamp GM Jr, Grantham JJ (2004) Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells. Kidney Int 66(3):964\u2013973","journal-title":"Kidney Int"},{"issue":"7","key":"10105_CR42","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1681\/ASN.V1171179","volume":"11","author":"K Hanaoka","year":"2000","unstructured":"Hanaoka K, Guggino WB (2000) cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells. J Am Soc Nephrol 11(7):1179\u20131187","journal-title":"J Am Soc Nephrol"},{"key":"10105_CR43","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1056\/NEJMoa1205511","volume":"367","author":"VE Torres","year":"2012","unstructured":"Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367:2407\u20132418","journal-title":"N Engl J Med"}],"container-title":["Purinergic Signalling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11302-025-10105-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11302-025-10105-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11302-025-10105-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T01:02:32Z","timestamp":1766451752000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11302-025-10105-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10105"],"URL":"https:\/\/doi.org\/10.1007\/s11302-025-10105-7","relation":{},"ISSN":["1573-9538","1573-9546"],"issn-type":[{"value":"1573-9538","type":"print"},{"value":"1573-9546","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]},"assertion":[{"value":"23 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article does not contain any studies with human participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}