{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T22:48:48Z","timestamp":1771627728820,"version":"3.50.1"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1993,7,1]]},"abstract":"<jats:p>Both amylin and calcitonin-gene-related neuropeptide (CGRP) activated adenylate cyclase activity in hepatocyte membranes around 5-fold in a dose-dependent fashion, with EC50 values of 120 +\/- 14 and 0.3 +\/- 0.14 nM respectively. Whereas amylin exhibited normal activation kinetics (Hill coefficient, h approximately 1), CGRP showed kinetics indicative of either multiple sites\/receptor species having different affinities for this ligand or a single receptor species exhibiting apparent negative co-operativity (h approximately 0.21). The CGRP antagonist CGRP-(8-37)-peptide inhibited adenylate cyclase stimulated by EC50 concentrations of either amylin or CGRP. Inhibition by CGRP-(8-37) was selective in that markedly lower concentrations were required to block the action of amylin (IC50 = 3 +\/- 1 nM) compared with that of CGRP itself (IC50 = 120 +\/- 11 nM). Dose-effect data for inhibition of CGRP action by CGRP-(8-37) showed normal saturation kinetics (h approximately 1), whereas CGRP-(8-37) inhibited amylin-stimulated adenylate cyclase activity in a fashion which was indicative of either multiple sites or apparent negative co-operativity (h approximately 0.24). Observed changes in the kinetics of inhibition by CGRP-(8-37) of CGRP, but not amylin-stimulated adenylate cyclase, at concentrations of agonists below their EC50 values militated against a model of two distinct populations of non-interacting receptors each able to bind both amylin and CGRP. A kinetic model is proposed whereby a single receptor, capable of being activated by both CGRP and amylin, obeys either a mnemonical kinetic mechanism or one of negative co-operativity with respect to CGRP but not to amylin. The relative merits of these two models are discussed together with a proposal suggesting that the activation of adenylate cyclase by various G-protein-linked receptors may be described by a mnemonical model mechanism.<\/jats:p>","DOI":"10.1042\/bj2930229","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:33:18Z","timestamp":1439242398000},"page":"229-236","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A mnemonical or negative-co-operativity model for the activation of adenylate cyclase by a common G-protein-coupled calcitonin-gene-related neuropeptide (CGRP)\/amylin receptor"],"prefix":"10.1042","volume":"293","author":[{"given":"M","family":"Bushfield","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Savage","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N J","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M D","family":"Houslay","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/293\/1\/229\/611414\/bj2930229.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/293\/1\/229\/611414\/bj2930229.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T22:28:46Z","timestamp":1637706526000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/293\/1\/229\/30206\/A-mnemonical-or-negative-co-operativity-model-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,7,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1993,7,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj2930229","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,7,1]]}}}