title: Protein kinase C involvement in homologous desensitization of delta-opioid receptor coupled to Gi1-phospholipase C activation in Xenopus oocytes.
abstract: We have developed the coexpression system of both delta-opioid receptor (DOR1) and M2-muscarinic receptor (M2) which mediate agonist-evoked currents due to common post-receptor mechanisms including Gi1 and phospholipase C (PLC) activation in Xenopus oocytes reconstituted with Gi1 alpha. The DOR1-currents by 100 nM D-Ser2-leu-enkephalin-Thr6 (DSLET) were selectively desensitized by 10 nM phorbol 12-myristate 13-acetate (PMA). The PMA-desensitization of DSLET-currents was abolished in the presence of calphostin C, a protein kinase C inhibitor, or reversed by an intracellular injection of calcineurin, a protein phosphatase 2B. When a higher concentration (3 microM) of DSLET was used, DSLET-currents were rapidly desensitized by repeated challenges of DSLET itself. However, repeated challenges of 10 microM ACh caused no influence on such DSLET- or M2-currents. The desensitization of DSLET-currents was selectively reversed by protein kinase C inhibitors. Similar results were also obtained with various delta-opioid agonists. These results suggest that protein kinase C is involved in the homologous desensitization of delta-opioid receptors.
mesh_terms: D000818:Animals; D004594:Electrophysiology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D007267:Injections; D009865:Oocytes / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012313:RNA / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D011976:Receptors, Muscarinic; D017465:Receptors, Opioid, delta; D004743:Enkephalin, Leucine; D012313:RNA; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate