{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:48:55Z","timestamp":1762145335049},"reference-count":0,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1991,12,1]]},"abstract":"<jats:p> The binding affinities of muscarinic antagonists were compared with their abilities to block carbachol (CCh)-mediated stimulation of Ca2+ mobilization and inhibition of isoproterenol-elicited adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat parotid cells. The binding of [3H]quinuclidinyl benzilate (QNB) to membranes was inhibited by antagonists with the following potencies (dissociation constant, nM): atropine (1.1) approximately 4-diphenylacetoxy-N-methylpiperidine methbromide (4-DAMP) (1.6) much greater than pirenzepine (136) greater than 11-[[2-[(diethylamino)methyl-1-piperidinyl]-acetyl]acetyl]-5,11- dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepine-6-one (AF-DX 116) (5,293). AF-DX 116 blocked Ca2+ mobilization and inhibition of cAMP accumulation with low affinities [inhibitory concentration at 50% (IC50) = 3150 and 6,528 nM, respectively], whereas 4-DAMP blocked these responses with considerably higher affinities (IC50 = 4.3 and 11.4 nM, respectively). Schild plots of 4-DAMP and AF-DX 116 antagonism of CCh-stimulated inositol trisphosphate accumulation showed inhibitor constant (Ki) values of 0.85 and 1,585 nM, respectively, whereas Schild plots of 4-DAMP, AF-DX 116, and methoctramine antagonism of CCh-induced inhibition of cAMP accumulation showed Ki values of 1.3, 1,585, and 2,754 nM, respectively. Preincubation of cells with 0.1 mM 3-isobutyl-1-methylxanthine did not prevent the capacity of CCh to inhibit cAMP accumulation. Pertussis toxin blocked the CCh-elicited and Gi-mediated inhibition of cAMP formation. Northern blot analysis showed the presence of mRNA for the M3, but not for the M2, subtype in parotid gland. An immunochemical procedure using m1-m5 specific antibodies was performed in parotid membranes and showed that the m3 receptor accounts for 93% of precipitable receptors. These data suggest that M3 receptors in the rat parotid are coupled to both the stimulation of Ca2+ mobilization and the inhibition of cAMP accumulation. <\/jats:p>","DOI":"10.1152\/ajpcell.1991.261.6.c1063","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T13:24:43Z","timestamp":1514121883000},"page":"C1063-C1073","source":"Crossref","is-referenced-by-count":98,"title":["Evidence that M3 muscarinic receptors in rat parotid gland couple to two second messenger systems"],"prefix":"10.1152","volume":"261","author":[{"given":"Y. S.","family":"Dai","sequence":"first","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. S.","family":"Ambudkar","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. J.","family":"Horn","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. K.","family":"Yeh","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. E.","family":"Kousvelari","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. J.","family":"Wall","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. P.","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. B.","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. J.","family":"Baum","sequence":"additional","affiliation":[{"name":"Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.1991.261.6.C1063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:46:02Z","timestamp":1718653562000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.1991.261.6.C1063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,12,1]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1991,12,1]]}},"alternative-id":["10.1152\/ajpcell.1991.261.6.C1063"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.1991.261.6.c1063","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,12,1]]}}}