{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:27:12Z","timestamp":1781105232469,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1982,7]]},"abstract":"\n We studied platelets of patients with the genetic disorder pseudohypoparathyroidism (PHP) to test whether the nucleotide-binding proteins mediating stimulation of adenylate cyclase (termed N\n s<\/jats:sub>\n ) are identical to those mediating inhibition of cyclase (termed N\n i<\/jats:sub>\n ). Functional responses to hormones that work through stimulation of adenylate cyclase are blunted in PHP patients. The erythrocytes of many of these patients (PHP-Ia) have previously been shown to have decreased N\n s<\/jats:sub>\n activity whereas those of other PHP patients (PHP-Ib) have normal N\n s<\/jats:sub>\n activity. We find that this decreased N\n s<\/jats:sub>\n activity (measured by the ability to restore adenylate cyclase activity to membranes prepared from S49 cyc\n -<\/jats:sup>\n cells) also occurs in the platelets of PHP-Ia but not of PHP-Ib patients. Platelets from both groups of patients accumulate less cAMP in response to prostacyclin than do platelets from control subjects. In contrast to the decreased N\n s<\/jats:sub>\n function in patients with PHP-Ia, we find that N\n i<\/jats:sub>\n function in platelets is similar in these patients and control subjects in several types of experiments: (\n i<\/jats:italic>\n ) epinephrine-mediated inhibition of prostacyclin-stimulated cAMP production in intact platelets; (\n ii<\/jats:italic>\n ) the affinity of platelet \u03b1\n 2<\/jats:sub>\n -adrenergic receptors for epinephrine, as determined by competition for [\n 3<\/jats:sup>\n H]yohimbine binding; (\n iii<\/jats:italic>\n ) the decrease in receptor affinity for epinephrine produced by Na\n +<\/jats:sup>\n and GTP; and (\n iv<\/jats:italic>\n ) the concentration dependence of GTP for decreasing the affinity of these receptors for epinephrine. Because N\n i<\/jats:sub>\n is expressed normally in platelets from patients that are genetically deficient in N\n s<\/jats:sub>\n , we conclude that N\n s<\/jats:sub>\n and N\n i<\/jats:sub>\n are likely to be distinct gene products.\n <\/jats:p>","DOI":"10.1073\/pnas.79.13.4193","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T04:51:33Z","timestamp":1149051093000},"page":"4193-4197","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":26,"title":["Platelets of pseudohypoparathyroid patients: Evidence that distinct receptor-cyclase coupling proteins mediate stimulation and inhibition of adenylate cyclase"],"prefix":"10.1073","volume":"79","author":[{"given":"Harvey J.","family":"Motulsky","sequence":"first","affiliation":[{"name":"Division of Pharmacology, M-013H, Department of Medicine, University of California at San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, M-013H, Department of Medicine, University of California at San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold S.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Mineral Metabolism Section, Medical and Research Services, Veterans Administration Medical Center, Los Angeles, California 91343"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Farfel","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Department of Medicine, Sheba Medical Center, Tel Hashomer, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry R.","family":"Bourne","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine and Pharmacology, University of California, San Francisco, California 94143."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Insel","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, M-013H, Department of Medicine, University of California at San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1982,7]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.79.13.4193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T11:26:10Z","timestamp":1649849170000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.79.13.4193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1982,7]]},"references-count":0,"journal-issue":{"issue":"13","published-print":{"date-parts":[[1982,7]]}},"alternative-id":["10.1073\/pnas.79.13.4193"],"URL":"https:\/\/doi.org\/10.1073\/pnas.79.13.4193","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1982,7]]},"assertion":[{"value":"1982-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}