{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:30:30Z","timestamp":1761744630263,"version":"3.41.0"},"reference-count":31,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1998,9,1]]},"abstract":"<jats:p>In the estrogen-treated rat myometrium, carbachol increased the generation of inositol phosphates by stimulating the muscarinic receptor-G<jats:sub>q<\/jats:sub>\/G<jats:sub>11<\/jats:sub>-phospholipase C-\u03b23 (PLC-\u03b23) cascade. Exposure to carbachol resulted in a rapid and specific (homologous) attenuation of the subsequent muscarinic responses in terms of inositol phosphate production, PLC-\u03b23 translocation to membrane, and contraction. Refractoriness was accompanied by a reduction of membrane muscarinic binding sites and an uncoupled state of residual receptors. Protein kinase C (PKC) altered the functionality of muscarinic receptors and contributed to the initial period of desensitization. A delayed phase of the muscarinic refractoriness was PKC independent and was associated with a downregulation of G<jats:sub>q<\/jats:sub>\u03b1\/G<jats:sub>11<\/jats:sub>\u03b1. Atropine failed to induce desensitization as well as G<jats:sub>q<\/jats:sub>\u03b1\/G<jats:sub>11<\/jats:sub>\u03b1 downregulation, indicating that both events involve active occupancy of the receptor. Prolonged exposure to A[Formula: see text] reduced subsequent A[Formula: see text] as well as carbachol-mediated inositol phosphate responses and similarly induced downregulation of G<jats:sub>q<\/jats:sub>\u03b1\/G<jats:sub>11<\/jats:sub>\u03b1. Data suggest that a decrease in the level of G<jats:sub>q<\/jats:sub>\u03b1\/G<jats:sub>11<\/jats:sub>\u03b1 is subsequent to its activation and may account for heterologous desensitization.<\/jats:p>","DOI":"10.1152\/ajpcell.1998.275.3.c636","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T17:53:19Z","timestamp":1514137999000},"page":"C636-C645","source":"Crossref","is-referenced-by-count":15,"title":["Carbachol-induced desensitization of PLC-\u03b2 pathway in rat myometrium: downregulation of G<sub>q<\/sub>\u03b1\/G<sub>11<\/sub>\u03b1"],"prefix":"10.1152","volume":"275","author":[{"given":"Sandrine","family":"Lajat","sequence":"first","affiliation":[{"name":"Signalisation et R\u00e9gulations Cellulaires, Centre National de la Recherche Scientifique, EP1088, Universit\u00e9 Paris-Sud, 91405 Orsay Cedex, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Harbon","sequence":"additional","affiliation":[{"name":"Signalisation et R\u00e9gulations Cellulaires, Centre National de la Recherche Scientifique, EP1088, Universit\u00e9 Paris-Sud, 91405 Orsay Cedex, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Tanfin","sequence":"additional","affiliation":[{"name":"Signalisation et R\u00e9gulations Cellulaires, Centre National de la Recherche Scientifique, EP1088, Universit\u00e9 Paris-Sud, 91405 Orsay Cedex, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2850529"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3220001"},{"key":"B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0026-895X(25)08650-X","volume":"46","author":"Bukhtiar H. 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