Activation of mu-opioid receptor modulates GABAA receptor-mediated currents in isolated spinal dorsal horn neurons.
Whole-cell voltage-clamp technique was used to examine the effects of a mu-opioid receptor agonist DAGO (Tyr-D-Ala-Gly-Me-Phe-Gly-ol-enkephalin) on GABA-induced currents in acutely isolated spinal dorsal horn (DH) neurons from laminae I-IV of young rats. We found that a bicuculline-sensitive GABA-induced current was potentiated by DAGO (0.5-500 nM), in a dose-dependent manner, in approximately 62% of the tested cells. The elevated GABA responses outlasted the period of DAGO application, and either recovered within 10 min after the removal of the peptide or persisted for up to 50 min. The potentiating effect of DAGO was reduced or prevented by naloxone and the mu-opioid receptor-selective antagonist beta-funaltrexamine. A similar enhancing effect on the membrane currents activated by administration of muscimol, a GABAA receptor-specific agonist, was produced by DAGO. In addition, a transient depression of GABA responses was observed in approximately 25% of the cells tested. These results indicate that the mu-opioid agonist DAGO modulates the sensitivity of postsynaptic GABAA receptors in a large proportion of spinal neurons from laminae I-IV, with the major effect being facilitation. The DAGO action could contribute to the regulation of the strength of primary afferent neurotransmission, including nociception.
Wang
R A
RA
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
Randić
M
M
D000200:Action Potentials / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008969:Molecular Sequence Data; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology*
D004745:Enkephalins; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009118:Muscimol; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; D001640:Bicuculline