{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:12:57Z","timestamp":1771632777477,"version":"3.50.1"},"reference-count":0,"publisher":"Proceedings of the National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1979,6]]},"abstract":"<jats:p>\n            In the supernatant (30,000 \u00d7\n            <jats:italic>g<\/jats:italic>\n            ) of frog erythrocyte homogenates, by using gel filtration we detected a protein that could bind [\n            <jats:sup>3<\/jats:sup>\n            H]dihydroalprenolol ([\n            <jats:sup>3<\/jats:sup>\n            H]DHA) with high affinity. This binding was greatly enhanced when the erythrocytes were preincubated with (-)-isoproterenol. After various periods of incubation with (-)-isoproterenol, the extent of the increase in the density of [\n            <jats:sup>3<\/jats:sup>\n            H]DHA binding sites in the cytosol was paralleled by a proportional decrease in the number of [\n            <jats:sup>3<\/jats:sup>\n            H]DHA binding sites in the corresponding pellet; both events peaked after 2-3 hr of incubation with (-)-isoproterenol. The\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>a<\/jats:sub>\n            of the (-)-isoproterenol-induced increase in [\n            <jats:sup>3<\/jats:sup>\n            H]DHA binding in cytosol and the decrease in this binding in the membrane ranged between 60 and 90 nM. The changes in the cytosol and particulate [\n            <jats:sup>3<\/jats:sup>\n            H]DHA binding sites were independent of RNA and protein synthesis. The increase in cytosol binding elicited by (-)-isoproterenol was blocked by exposure of the cells to (-)-alprenolol which\n            <jats:italic>per se<\/jats:italic>\n            failed to change the cytosol binding of [\n            <jats:sup>3<\/jats:sup>\n            H]DHA. Scatchard analysis revealed that the enhanced [\n            <jats:sup>3<\/jats:sup>\n            H]DHA binding to cytosol material was due to a 4-fold increase in the\n            <jats:italic>B<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            with little or no change in\n            <jats:italic>K<\/jats:italic>\n            <jats:sub>d<\/jats:sub>\n            (\u22489 nM). Binding displacement data show that these soluble [\n            <jats:sup>3<\/jats:sup>\n            H]DHA binding sites resemble the surface membrane recognition sites. Moreover, the ability of various \u03b2-adrenergic agents to increase [\n            <jats:sup>3<\/jats:sup>\n            H]DHA binding to cytosol after they were incubated with frog erythrocytes paralleled their affinity for membrane-bound \u03b2 receptors. These findings support the view that the \u03b2-adrenergic receptor desensitization caused by prolonged exposure to (-)-isoproterenol is due, at least in part, to an internalization of the recognition site of \u03b2-adrenergic receptors.\n          <\/jats:p>","DOI":"10.1073\/pnas.76.6.3024","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:59:16Z","timestamp":1149062356000},"page":"3024-3028","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":101,"title":["Evidence for internalization of the recognition site of \u03b2-adrenergic receptors during receptor subsensitivity induced by (-)-isoproterenol"],"prefix":"10.1073","volume":"76","author":[{"given":"De-Maw","family":"Chuang","sequence":"first","affiliation":[{"name":"Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D. C. 20032"}]},{"given":"E.","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D. C. 20032"}]}],"member":"341","published-online":{"date-parts":[[1979,6]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.76.6.3024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T15:23:29Z","timestamp":1649863409000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.76.6.3024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1979,6]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1979,6]]}},"alternative-id":["10.1073\/pnas.76.6.3024"],"URL":"https:\/\/doi.org\/10.1073\/pnas.76.6.3024","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1979,6]]},"assertion":[{"value":"1979-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}