{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T20:08:57Z","timestamp":1772309337647,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T00:00:00Z","timestamp":1416787200000},"content-version":"vor","delay-in-days":0,"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":[[2015,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Adenylyl cyclase (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>) is a key signalling enzyme for many <jats:styled-content style=\"fixed-case\">GPCRs<\/jats:styled-content> and catalyses the conversion of <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> which, in turn, is a crucial determinant of many biological responses. \u03b2\u2010Adrenoceptor agonists are prescribed as bronchodilators for asthma and chronic obstructive pulmonary disease, and it is commonly assumed that they elicit their actions via <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>\u2010dependent production of <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>. However, empirical evidence in support of this is lacking and the exact mechanism by which these drugs acts remains elusive. This is partly due to the existence of at least 10 different isoforms of AC and the absence of any truly selective pharmacological inhibitors. Here, we have used genetically modified mice and model systems to establish the role of <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content> isoforms in the airway responses to \u03b2\u2010adrenoceptor agonists.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Receptors mediating responses to \u03b2\u2010adrenoceptor agonists in airway smooth muscle (<jats:styled-content style=\"fixed-case\">ASM<\/jats:styled-content>) and sensory nerve were identified in isolated tissue systems. Expression of <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for the <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content> isoforms in <jats:styled-content style=\"fixed-case\">ASM<\/jats:styled-content> and neurones was determined by <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>. Functional responses were assessed in <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content> isoform <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice and wild\u2010type controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Airway and vagal tissue expressed <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for various isoforms of <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>. AC6 was the most prominent isoform. Responses to \u03b2\u2010adrenoceptor agonists in tissues from AC6 KO mice were virtually abolished.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AC6<\/jats:styled-content> played a critical role in relaxation of <jats:styled-content style=\"fixed-case\">ASM<\/jats:styled-content> to \u03b2<jats:sub>1<\/jats:sub>\u2010adrenoceptor agonists and in modulation of sensory nerves by \u03b2<jats:sub>1\u20103<\/jats:sub>\u2010adrenoceptor agonists. These results further unravel the signalling pathway of this extensively prescribed class of medicine.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12905","type":"journal-article","created":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T07:21:05Z","timestamp":1410333665000},"page":"131-141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The role of adenylyl cyclase isoform 6 in \u03b2\u2010adrenoceptor signalling in murine airways"],"prefix":"10.1111","volume":"172","author":[{"given":"Mark A","family":"Birrell","sequence":"first","affiliation":[{"name":"Respiratory Pharmacology, National Heart and Lung Institute, Faculty of Medicine Imperial College London  London UK"},{"name":"MRC\u2010Asthma UK Centre in Allergic Mechanisms of Asthma  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara J","family":"Bonvini","sequence":"additional","affiliation":[{"name":"Respiratory Pharmacology, 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