{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:54:38Z","timestamp":1773460478707,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:p><jats:bold>Background and purpose:<\/jats:bold> In human airways, muscarinic acetylcholine receptors (mAChRs) exert a predominant role in the control of airways resistance and anti\u2010muscarinic agents are currently included in the pharmacological treatment of chronic obstructive pulmonary disease (COPD). However, the development of more effective mAChR antagonists is hampered by considerable species variability in the ultrastrucural and functional control of airway smooth muscle, making extrapolation of any particular animal model questionable. This study was designed to characterize the mAChRs in a bronchial preparation from pigs, animals considered to provide close models of human biology.<\/jats:p><jats:p><jats:bold>Experimental approach:<\/jats:bold> Smooth muscle bronchial strips were examined by electron microscopy in order to compare their neuromuscular structure with that of human bronchi and used to study the affinity of a series of selective mAChR antagonists, estimated as pK<jats:sub>i<\/jats:sub>s in competition binding assays with NMS and pA<jats:sub>2,<\/jats:sub> by Schild analysis, in contractile experiments.<\/jats:p><jats:p><jats:bold>Key results:<\/jats:bold> Pharmacodynamic binding parameters and affinity profiles of a series of antagonists were consistent with the presence of a majority of M<jats:sub>2\u2003<\/jats:sub>mAChRs along with a minor population of M<jats:sub>3\u2003<\/jats:sub>mAChRs. Functionally, the highly significant correlation between postjunctional pA<jats:sub>2<\/jats:sub> affinities and corresponding affinity constants at human recombinant M<jats:sub>1<\/jats:sub>\u2013M<jats:sub>5<\/jats:sub> subtypes indicated that smooth muscle contraction in porcine bronchi, as in human bronchi, was dependent on the M<jats:sub>3<\/jats:sub> subtype.<\/jats:p><jats:p><jats:bold>Conclusion and implications:<\/jats:bold> Based on the characterization of mAChRs, isolated porcine bronchi provide an additional experimental model for development of mAChR antagonists for the treatment of human airway dysfunctions.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2008) <jats:bold>154<\/jats:bold>, 1611\u20131618; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.208\">10.1038\/bjp.2008.208<\/jats:ext-link>; published online 2 June 2008<\/jats:p>","DOI":"10.1038\/bjp.2008.208","type":"journal-article","created":{"date-parts":[[2008,6,2]],"date-time":"2008-06-02T10:15:03Z","timestamp":1212401703000},"page":"1611-1618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Isolated porcine bronchi provide a reliable model for development of bronchodilator anti\u2010muscarinic agents for human use"],"prefix":"10.1111","volume":"154","author":[{"given":"G","family":"D'Agostino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A M","family":"Condino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Gioglio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Zonta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Tonini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"issue":"2","key":"e_1_2_8_2_1","first-page":"S1","article-title":"Guide to Receptors and Channels (GRAC), 3rd edn","volume":"153","author":"Alexander SPH","year":"2008","journal-title":"Br J Pharmacol"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_8_4_1","first-page":"1289","article-title":"Neural control of human airways in health and disease","volume":"134","author":"Barnes PJ","year":"1986","journal-title":"Am Rev Respir Dis"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/136.4_Pt_2.S42"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200409-045MS"},{"key":"e_1_2_8_7_1","first-page":"625","article-title":"Characterisation of muscarinic receptor subtypes in human peripheral lung","volume":"244","author":"Bloom JW","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_8_1","first-page":"469","article-title":"Antagonist binding properties of five cloned muscarinic receptors expressed in CHO\u2010K1 cells","volume":"35","author":"Buckley NJ","year":"1989","journal-title":"Mol Pharmacol"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00038.2002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1998.tb01469.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(86)90034-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703080"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00166956"},{"key":"e_1_2_8_15_1","first-page":"459","article-title":"Immunological detection of muscarinic receptors subtypes proteins (m1\u2010m5) in rabbit peripheral lung","volume":"40","author":"D\u00f6rje F","year":"1991","journal-title":"Mol Pharmacol"},{"key":"e_1_2_8_16_1","first-page":"727","article-title":"Antagonist binding profiles of five cloned human muscarinic receptor subtypes","volume":"256","author":"D\u00f6rje F","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_17_1","first-page":"531","article-title":"Muscarinic receptor subtypes and smooth muscle function","volume":"48","author":"Eglen RM","year":"1996","journal-title":"Pharmacol Rev"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12983.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703276"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.30.2.162"},{"key":"e_1_2_8_21_1","first-page":"309","article-title":"Characterisation of muscarinic receptors in human, guinea pig and rat lung","volume":"250","author":"Gies JP","year":"1989","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-73"},{"key":"e_1_2_8_23_1","first-page":"378","article-title":"Ligand binding properties of muscarinic acetylcholine receptor subtypes (m1\u2010m5) expressed in baculovirus\u2010infected insect cells","volume":"274","author":"Guo ZD","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_24_1","first-page":"L642","article-title":"Characterisation of muscarinic receptor subtypes in pig airways: radioligand binding and northern blotting studies","volume":"266","author":"Haddad EB","year":"1994","journal-title":"Am J Physiol"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.145.5.927"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/15.2.108"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701048"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00585-8"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00004977"},{"key":"e_1_2_8_30_1","first-page":"805","article-title":"Characterisation of the muscarinic M4 binding sites in in rabbit lung, chicken heart, and NG108 15 cells","volume":"38","author":"Lazareno S","year":"1990","journal-title":"Mol Pharmacol"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(94)90075-2"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90462-7"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/141.6.1559"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/7.3.344"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(93)90624-C"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.3.7663798"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2004.03.001"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0952-0600(90)90009-8"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90391-T"},{"key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1152\/jappl.1988.65.2.721","article-title":"Airways epithelium modulates the responsiveness of porcine bronchial smooth musle","volume":"65","author":"Stuart\u2010Smith K","year":"1988","journal-title":"J Appl Physiol"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.154.1.8680697"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(87)90092-9"},{"key":"e_1_2_8_43_1","first-page":"760","article-title":"Autoradiographic visualization of muscarinic receptors in human bronchi","volume":"244","author":"Van Koppen CJ","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00634245"},{"key":"e_1_2_8_45_1","first-page":"1293","article-title":"Pharmacological characterisation of the muscarinic receptor subtype mediating contraction of human peripheral airways","volume":"274","author":"Watson N","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_46_1","first-page":"149","article-title":"Development of antisera selective for m4 and m5 muscarinic cholinergic receptors: distribution of m4 and m5 receptors in rat brain","volume":"43","author":"Yasuda RP","year":"1993","journal-title":"Mol Pharmacol"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fbjp.2008.208","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fbjp.2008.208","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/bjp.2008.208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T15:38:56Z","timestamp":1697125136000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/bjp.2008.208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8]]},"references-count":45,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["10.1038\/bjp.2008.208"],"URL":"https:\/\/doi.org\/10.1038\/bjp.2008.208","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}