Carbachol-induced desensitization of PLC-β pathway in rat myometrium: downregulation of Gqα/G11α
| Autor: | Zahra Tanfin, Sandrine Lajat, S. Harbon |
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| Rok vydání: | 1998 |
| Předmět: | |
| Zdroj: | American Journal of Physiology-Cell Physiology. 275:C636-C645 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1998.275.3.c636 |
| Popis: | In the estrogen-treated rat myometrium, carbachol increased the generation of inositol phosphates by stimulating the muscarinic receptor-Gq/G11-phospholipase C-β3 (PLC-β3) cascade. Exposure to carbachol resulted in a rapid and specific (homologous) attenuation of the subsequent muscarinic responses in terms of inositol phosphate production, PLC-β3 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 Gqα/G11α. Atropine failed to induce desensitization as well as Gqα/G11α 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 Gqα/G11α. Data suggest that a decrease in the level of Gqα/G11α is subsequent to its activation and may account for heterologous desensitization. |
| Databáze: | OpenAIRE |
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