The role of the ORL1 receptor in the modulation of spinal neurotransmission by nociceptin/orphanin FQ and nocistatin.
Nociceptin/orphanin FQ and nocistatin are two neuropeptides with opposing effects on spinal neurotransmission and nociception. Nociceptin/orphanin FQ selectively suppresses excitatory glutamatergic neurotransmission, while nocistatin selectively interferes with glycinergic and gamma-aminobutyric acid (GABA)-ergic transmission. Here, we performed whole-cell patch-clamp recordings from superficial rat spinal cord dorsal horn neurons to investigate the role of the opioid receptor-like (ORL)1 receptor for modulatory actions of these peptides. The partial ORL1 receptor antagonist [phe1psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)NH(2) competitively reversed the effects of nociceptin/orphanin FQ on excitatory neurotransmission (estimated pA(2) 6.43), but left the suppression of inhibitory synaptic transmission by nocistatin unaffected. These results indicate that the inhibitory action of nociceptin/orphanin FQ on glutamatergic transmission is mediated via ORL1 receptors, while nocistatin acts via a different so far unidentified receptor.
Ahmadi
S
S
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054, Erlangen, Germany.
Liebel
J T
JT
Zeilhofer
H U
HU
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D018847:Opioid Peptides / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000701:Analgesics, Opioid; D018847:Opioid Peptides; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C111148:nocistatin; C000722285:Oprl1 protein, rat