Depression of glutamatergic transmission by nociceptin in the neonatal rat hemisected spinal cord preparation in vitro.
The present study explored the action of nociceptin, the putative endogenous ligand for the orphan opioid receptor (ORL1), on the rat hemisected spinal cord preparation. Electrical stimulation of a dorsal root evokes a glutamatergic population ventral root potential (DR-VRP) in the corresponding ventral root. Low intensity stimulation evokes two A fibre-mediated components; a compound action potential of motoneurones superimposed on a population e.p.s.p. (excitatory postsynaptic potential); at higher stimulus intensities sufficient to activate C fibres a more prolonged population e.p.s.p. is evoked. All three components were depressed by nociceptin in a concentration-dependent manner with IC50 values (s.e.mean) of 119 +/- 2 nM (n = 4), 241 +/- 3 nM (n = 4) and 32 +/- 2 nM (n = 4), respectively. The depressant actions of nociceptin (30 nM and 300 nM) were not reversed by the opioid antagonist naloxone (1 microM). Nociceptin (100 nM and 300 nM) had no effect on the afferent volleys in the dorsal root. Nociceptin therefore appears to be acting as an inhibitory peptide at the spinal level through a naloxone-insensitive opioid receptor.
Faber
E S
ES
Department of Pharmacology, School of Medical Sciences, Bristol.
Chambers
J P
JP
Evans
R H
RH
Henderson
G
G
D000595:Amino Acid Sequence; D000818:Animals; D003864:Depression, Chemical; D004210:Dissection; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D011957:Receptors, Opioid / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D017470:Receptors, Glutamate; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat