Prolonged stimulation of insulin secretion by depolarization and Ca2+ influx regularly leads to a reversible state of decreased secretory responsiveness to nutrient and nonnutrient stimuli. This state is termed "desensitization." The onset of desensitization may occur within 1 h of exposure to depolarizing stimuli. Desensitization by exposure to sulfonylureas, imidazolines, or quinine produces ...

Type 1 parathyroid hormone receptor (PTH1R) activation, desensitization, internalization, and recycling proceed in a cyclical manner. The Na(+)/H(+) exchange regulatory factor 1 (NHERF1) is a cytoplasmic adapter protein that regulates trafficking and signaling of several G protein-coupled receptors (GPCRs) including the PTH1R. The mineral ion wasting and bone phenotype of NHERF1-null mice sugge...

-Opioid receptors (MORs) activate G-protein coupled inwardly rectifying potassium (GIRK) channels. The peptide agonist [D-Ala, NMe-Phe, Gly-ol]enkephalin (DAMGO), but not the alkaloid morphine (MS), leads to acute desensitization of this response. Furthermore, DAMGO, as opposed to MS, triggers rapid internalization of MORs. Given this dichotomy, we probed the relationship between receptor inter...

Differences involving serine residues in the sequence of the carboxyl-terminal tail of type 1 angiotensin II (Ang II) receptor subtypes AT(1A) and AT(1B) suggest differences in desensitization ability. We examined the Ang II-induced homologous desensitization patterns of both receptor subtypes in freshly isolated renal structures: glomerulus (Glom), afferent arteriole, and cortical thick ascend...

Benzodiazepines are neuromodulatory drugs that potentiate GABA-mediated conductance increases. We report the findings of an investigation into the effect of a full benzodiazepine-positive modulator (agonist), chlordiazepoxide (CDPX), on desensitization of the GABA response in chick spinal cord neurons maintained in primary monolayer cell culture. GABA application initially increases cell conduc...

Sustained stimulation of the b -adrenoceptor leads to a desensitization of the receptor-mediated adenylyl cyclase stimulation. While 2 desensitization promoted by nanomolar concentrations of isoproterenol involves the phosphorylation of the b -adrenoceptor by protein 2 kinase A alone, both protein kinase Aand b-adrenoceptor kinase-mediated phosphorylation leading to the binding of b-arrestin co...

The homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase induced by lutropin (LH) was characterized with the aid of forskolin and cholera toxin. Forskolin stimulated cyclic AMP production in a dose-dependent manner, with linear kinetics up to 2 h. Forskolin also potentiated the action ofLH on cyclicAMP production, but was only additive with cholera toxin. Prei...

Yan, Weihong, Chinnaswamy Tiruppathi, Hazel Lum, Renli Qiao, and Asrar B. Malik. Protein kinase Cb regulates heterologous desensitization of thrombin receptor (PAR-1) in endothelial cells. Am. J. Physiol. 274 (Cell Physiol. 43): C387–C395, 1998.—We studied the effects of protein kinase C (PKC) activation on endothelial cell surface expression and function of the proteolytically activated thromb...