Postsynaptic mechanisms underlying responsiveness of amygdaloid neurons to nociceptin/orphanin FQ.
Effects of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor (ORL), were investigated in the rat lateral (AL) and central (ACe) amygdala in vitro. Approximately 98% of presumed projection neurons in the AL responded to N/OFQ with an increase in inwardly rectifying potassium conductance, resulting in an impairment in cell excitability. Half-maximal effects were obtained at 30.6 nM; the Hill coefficient was 0.63. In the ACe, 31% of the cells displayed responses similar to that in the AL, 44% were nonresponsive, and 25% responded with a small potassium current with a linear current-voltage relationship. Responses to N/OFQ were reduced by 100 microM Ba2+, were insensitive to 10 microM naloxone, and were blocked by a selective ORL antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 (IC50 = 760 nM). Involvement of G-proteins was indicated by irreversible effects and blockade of action of N/OFQ during intracellular presence of GTP-gamma-S (100 microM) and GDP-beta-S (2 mM), respectively, and prevention of responses after incubation in pertussis toxin (500 ng/ml). These mechanisms may contribute to the role of N/OFQ in the reduction of fear responsiveness and stress that have recently been suggested on the basis of histochemical and behavioral studies.
Institut für Physiologie, Otto-von-Guericke-Universität, D-39120 Magdeburg, Germany.
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000737:chemistry / Q000166:cytology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D018847:Opioid Peptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000493:pharmacokinetics; D015221:Potassium Channels / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D020318:Rats, Long-Evans; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology*; D013569:Synapses / Q000737:chemistry / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D001464:Barium; D019204:GTP-Binding Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011188:Potassium; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C034883:guanosine 5'-O-(2-thiotriphosphate); C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C000722285:Oprl1 protein, rat