Opioid peptides modulate the response of neurons of the superficial laminae of the rat spinal dorsal horn to GABA.
The modulatory effects of methionine-enkephalin (M-ENK) and selective opioid-receptor agonists on GABA-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae of the rat spinal dorsal horn using nystatin-perforated patch recording configuration under voltage-clamp conditions. The results show that: (1). GABA acted on GABA(A) receptors and elicited inward Cl(-) currents (I(GABA)) at -60 mV; (2). M-ENK depressed I(GABA) in approximately 65% of the tested neurons and potentiated I(GABA) in approximately 15% of the neurons tested; (3). the agonists of mu-, kappa-, and delta-opioid receptors-[D-AIa(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), dynorphin-A (Dyn-A), and [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) also depressed the I(GABA), and the order of agonist potency was DAMGO>Dyn-A>DPDPE; and (4) naloxone blocked the inhibitory effects of M-ENK on I(GABA). The antagonists of mu-, kappa-, and delta-opioid receptors-beta-funaltrexamine (beta-FNA), nor-binaltorphimine (nor-BNI), and naltrindole (NTI) prevented the DAMGO-, Dyn-A-, and DPDPE-induced depression of I(GABA). The results suggest that M-ENK downregulates I(GABA) principally through mu- and kappa-opioid receptors, and thus exerts its modulating effects indirectly on the transmission of noxious information at the spinal level.
Li
Hui
H
Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China.
Wu
Le
L
Li
Yun-Qing
YQ
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine