title: [ROLE PHOSPHOINOSITID SIGNALING PATHWAY IN OPIOIDS CONTROL OF P2X3 RECEPTORS IN THE PRIMARY SENSORY NEURONS].
abstract: Homomeric P2X3 receptors expressed in primary nociceptive neurons are crucial elements in the pain signal generation. In turn, opioid system regulates the intensity of this signal in both CNS and PNS. Here we describe the effects of opioids on P2X3 receptors in DRG neurons studied by using patch clamp technique. Activation of G-protein coupled opioid receptors by endogenous opioid Leu-enkephalin (Leu), resulted in the two opposite effects on P2X3 receptor-mediated currents (P2X3 currents). In particular, application of 1 µM Leu lead to the complete inhibition of P2X3 currents. However, after pretreatment of the neurons with a Gi/o-protein inhibitor pertussis toxin (PT), the same concentration of Leu caused facilitation of P2X3 currents. PLC inhibitor U-73122 at concentration of 1 µM completely eliminated both facilitating and inhibitory effects of Leu on P2X3 currents. Thus, opioid receptor agonists cause two oppositely directed effects on P2X3 receptors in DRG neurons of rats and both of them are mediated through PLC signaling pathway. Our results point to a possible molecular basis of the mechanism for the well-known transition inhibitory action of opioids (analgesia) to facilitating (hyperalgesia).
authors.forename: V B
authors.initials: VB
authors.lastname: Kulyk
authors.forename: I V
authors.initials: IV
authors.lastname: Chizhmakov
authors.forename: T M
authors.initials: TM
authors.lastname: Volkova
authors.forename: O P
authors.initials: OP
authors.lastname: Maximyuk
authors.forename: O A
authors.initials: OA
authors.lastname: Krishtal
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004745:Enkephalins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D009270:Naloxone / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000633:toxicity; D010716:Phosphatidylinositols / Q000378:metabolism*; D061251:Primary Cell Culture; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058477:Receptors, Purinergic P2X3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D004745:Enkephalins; D004791:Enzyme Inhibitors; D004963:Estrenes; D010716:Phosphatidylinositols; D011760:Pyrrolidinones; D058477:Receptors, Purinergic P2X3; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D009270:Naloxone; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019311:Staurosporine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate