Orphanin FQ-induced outward current in rat hippocampus.
Orphanin FQ (OFQ) is a heptadecapeptide that structurally resembles opioid peptides. It has been demonstrated that the moderate density of binding sites of OFQ were localized in the hippocampus and that the expression of OFQ receptor in the hippocampus have an important role in learning and memory. This study was designed to investigate whether activation of the OFQ receptor could induced hyperpolarization in the cultured hippocampus neurons in rats. In the current clamp mode, the application of OFQ (10(-8)-10(-5) M) hyperpolarized the membranes in cultured hippocampus neurons in a concentration-dependent manner. Moreover, in the voltage clamp mode, application of OFQ (10(-6) M) induced outward current in hippocampus CA3 pyramidal neurons. In the presence of TTX (3x10(-7) M), the average maximal amplitude of the outward current deflection induced by OFQ (10(-6) M) at -60 mV of a holding potential was 24.7+/-0.54 pA. The OFQ-induced current reversed at -99.06+/-3.80 mV (3 mM), which was quite close to the K(+) equilibrium potential as calculated by the Nernst equation (E(k)=-96.08 mV, 3 mM) for K(+) in our standard solution. This suggests that OFQ-induced current was mediated by K(+) ion. It has been demonstrated that [Phe(1)psi(CH(2)-NH)Gly(2)]Nociceptin(1-13)NH(2)) (a pseudopeptide analog of nociceptin), and nocistatin are selective antagonists of OFQ. OFQ (10(-6) M)-induced outward current was antagonized by application of [Phe(1)psi(CH(2)-NH)Gly(2)]Nociceptin(1-13)NH(2) (10(-5) M). In contrast, OFQ-induced outward current was not antagonized by application of nocistatin (10(-5) M). These results indicates that there is the physiological functioning receptor of OFQ in the hippocampus.
Amano
T
T
Department of Pharmacology, Hiroshima University School of Medicine, Hiroshima, Japan.
Matsubayashi
H
H
Tamura
Y
Y
Takahashi
T
T
D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018847:Opioid Peptides; D010446:Peptide Fragments; D011188:Potassium; D015221:Potassium Channels; D011957:Receptors, Opioid; D013779:Tetrodotoxin; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C111148:nocistatin; C000722285:Oprl1 protein, rat