{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:44:59Z","timestamp":1790048699580,"version":"4.0.1"},"reference-count":40,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The diverse cellular changes brought about by the expression of a constitutively active receptor are poorly understood. QBI-human embryonic kidney 293A cells stably expressing the constitutively active N111G-AT1 receptor (N111G cells) showed elevated levels of inositol phosphates and frequent spontaneous intracellular Ca2+ oscillations. Interestingly, Ca2+ transients triggered with maximal doses of angiotensin II were much weaker in N111G cells than in wild-type cells. These blunted responses were observed independently of the presence or absence of extracellular Ca2+ and were also obtained when endogenous muscarinic and purinergic receptors were activated, revealing a heterologous desensitization process. The desensitized component of the Ca2+ signaling cascade was neither the G protein Gq nor phospholipase C. The intracellular Ca2+ store of N111G cells and their mechanism of Ca2+ entry also appeared to be intact. The most striking adaptive response of N111G cells was a down-regulation of their inositol 1,4,5-trisphosphate receptor (IP3R) as revealed by reduced IP3-induced Ca2+ release, lowered [3H]IP3 binding capacity, diminished IP3R immunoreactivity, and accelerated IP3R degradation involving the lysosomal pathway. Treatment with the inverse agonist EXP3174 reversed the desensitized phenotype of N111G cells. Down-regulation of IP3R represents a reversible adaptive response to protect cells against the adverse effects of constitutively active Ca2+-mobilizing receptors.<\/jats:p>","DOI":"10.1210\/me.2003-0488","type":"journal-article","created":{"date-parts":[[2004,8,27]],"date-time":"2004-08-27T00:13:06Z","timestamp":1093565586000},"page":"2967-2980","source":"Crossref","is-referenced-by-count":24,"title":["Down-Regulation of Inositol 1,4,5-Trisphosphate Receptor in Cells Stably Expressing the Constitutively Active Angiotensin II N111G-AT1 Receptor"],"prefix":"10.1210","volume":"18","author":[{"given":"Mannix","family":"Auger-Messier","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universite\u0301 de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Arguin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universite\u0301 de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Chaloux","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universite\u0301 de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Leduc","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universite\u0301 de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Escher","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universite\u0301 de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetan","family":"Guillemette","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universite\u0301 de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071616344295100_R1","first-page":"415","article-title":"International union of pharmacology. 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