{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:45:48Z","timestamp":1762145148153},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,8,1]]},"abstract":"<jats:p>The \u03b11-adrenergic agonist phenylephrine stimulated phospholipase D (PLD) activity in Rat 1 fibroblasts transfected to express either the wild-type hamster \u03b11B-adrenoceptor or a constitutively active mutant (CAM) form of this receptor. The EC50 for agonist stimulation of PLD activity was substantially lower at the CAM receptor than at the wild-type receptor as previously noted for phenylephrine stimulation of phosphoinositidase C activity. Sustained treatment of cells expressing the CAM \u03b11B-adrenoceptor with phentolamine resulted in a marked up-regulation in levels of this receptor with half-maximal effects produced within 24 h and with an EC50 of approx. 40 nM. Such an up-regulation could be produced with a range of other ligands generally viewed as \u03b11-adrenoceptor antagonists but equivalent treatment of cells expressing the wild-type \u03b11B-adrenoceptor was unable to mimic these effects. After sustained treatment of the CAM \u03b11B-adrenoceptor expressing cells with phentolamine, basal PLD activity was increased and phenylephrine was now able to stimulate PLD activity to greater levels than in vehicle-treated CAM \u03b11B-adrenoceptor-expressing cells. The EC50 for phenylephrine stimulation of PLD activity was not altered, however, by phentolamine pretreatment and the associated up-regulation of the receptor. After phentolamine-induced up-regulation of basal PLD activity, a range of \u03b11-antagonists were shown to possess the characteristics of inverse agonists of the CAM \u03b11B-adrenoceptor as they were able to substantially decrease the elevated basal PLD activity.<\/jats:p>","DOI":"10.1042\/bj3250733","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:55:16Z","timestamp":1439243716000},"page":"733-739","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Up-regulation of the levels of expression and function of a constitutively active mutant of the hamster \u03b11B-adrenoceptor by ligands that act as inverse agonists"],"prefix":"10.1042","volume":"325","author":[{"given":"Tae Weon","family":"LEE","sequence":"first","affiliation":[{"name":"Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K."}]},{"given":"Susanna","family":"COTECCHIA","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Toxicologie, Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Lausanne, Lausanne, Switzerland"}]},{"given":"Graeme","family":"MILLIGAN","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K."}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/325\/3\/733\/625111\/bj3250733.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/325\/3\/733\/625111\/bj3250733.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:26:06Z","timestamp":1637713566000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/325\/3\/733\/33488\/Up-regulation-of-the-levels-of-expression-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1997,8,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3250733","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,8,1]]}}}