Metabotropic glutamate receptors (mGluRs) coupled to phosphoinositide hydrolysis desensitize in response to prolonged or repeated agonist exposure, and evidence suggests that this involves activation of protein kinase C (PKC). The present studies were undertaken to determine if cloned mGluR5 undergoes similar PKC-mediated desensitization and to investigate the molecular mechanism underlying PKC...

The effect of specific competitive inhibitors of aminoacyl-tRNA synthetase on thyrotropin (TSH) desensitization in human thyroid cell monolayers was examined. Thyroid cells were preincubated with o r without 60 milliunits/ml of TSH for 16 h at 37 “C in histidinefree medium supplemented with either 2 m~ histidinol or 2 mM histidine (control medium). All cells were then exposed to TSH for 30 min ...

Recent studies have demonstrated that in vivo administration of 1-deamino-8-D-arginine-vasopressin, an analog of arginine-8-vasopressin, induces homologous desensitization to vasopressin in the thick ascending limb of the loop of Henle. Desensitization has been documented by a decreased physiological response to vasopressin in vivo and by a reduced cAMP accumulation in the cortical thick ascend...

Mu-opioid receptors (MORs) activate G-protein coupled inwardly rectifying potassium (GIRK) channels. The peptide agonist [D-Ala(2), NMe-Phe(4), Gly(5)-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 rec...

Ionotropic glutamate receptors from the AMPA and kainate subfamilies share many functional and structural features, but it is unclear whether this similarity extends to the molecular mechanisms underlying receptor desensitization. The current model for desensitization in AMPA receptors involves the rearrangement of dimers formed between subunit agonist binding domains. Key evidence for this has...

It is hypothesized that desensitization of neuronal nicotinic acetylcholine receptors (nAChRs) induced by chronic exposure to nicotine initiates upregulation of nAChR number. To test this hypothesis directly, oocytes expressing alpha4beta2 receptors were chronically incubated (24-48 hr) in nicotine, and the resulting changes in specific [3H]nicotine binding to surface receptors on intact oocyte...

P2X ion channels have been functionally characterized from a range of eukaryotes. Although these receptors can be broadly classified into fast and slow desensitizing, the molecular mechanisms underlying current desensitization are not fully understood. Here, we describe the characterization of a P2X receptor from the cattle tick Boophilus microplus (BmP2X) displaying extremely slow current kine...

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...