[Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) does not antagonize orphaninFQ/nociceptin-induced prolactin release.
The specificity of the orphaninFQ (OFQ)/nociceptin (N)-induced prolactin increase was determined in male and female rats by pretreating animals with different doses of [Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2), a compound originally reported to be a specific OFQ/N antagonist. In addition, the effect of naloxone pretreatment on OFQ/N-induced prolactin release was examined to determine if OFQ/N's effects were mediated by opiate receptors. Furthermore, dose response studies using [Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) only were performed to determine potential agonist activity of this drug. Finally, growth hormone (GH) levels were determined as an index of specificity of the prolactin response. Our results confirm previous findings that OFQ/N potently stimulates prolactin release and that a gender difference exists in the magnitude of the response, with females showing a much greater response than male rats. The endocrine response is specific because OFQ/N potently stimulated prolactin, but not GH secretion. The prolactin response is not mediated by actions at opiate receptors because naloxone did not inhibit OFQ/N's effects on prolactin release. However, [Phe(1)Psi(CH(2)-NH) Gly2]NC(1-13) NH(2) did not antagonize OFQ/N's effects on prolactin release. Indeed, this drug acted as a potent agonist. Demonstrating pharmacological specificity of OFQ/N's effects on prolactin release awaits the development of more selective, specific antagonists.
Bryant
Winnifred
W
Department of Zoology, Center for Neuroscience, Miami University, Oxford, OH 45056, USA.
Callahan
Phyllis
P
Murphree
Emily
E
Janik
James
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism; D012727:Sex Characteristics; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009270:Naloxone; D009292:Narcotic Antagonists; D009294:Narcotics; D018847:Opioid Peptides; D010446:Peptide Fragments; D011388:Prolactin; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C000722285:Oprl1 protein, rat