Opiate suppression of LH secretion involves central receptors different from those mediating opiate effects on prolactin secretion.
The involvement of mu- and kappa-opiate receptors in the regulation of LH and prolactin secretion was investigated in long-term ovariectomized rats using selective opiate receptor agonists and antagonists. The mu-agonists morphine and [D-Ala2,MePhe4,Gly5-ol]-enkephalin (DAGO) suppressed LH levels in a dose-related manner. The benzomorphane (-)-5,9-dimethyl-2'-hydroxy-2-(tetrahydrofurfuryl)-6,7-benzomorphan tartrate (MR 2034; a designated kappa-agonist) also suppressed LH levels, whereas another benzomorphane kappa-agonist (-)-5,9-dimethyl-2'-hydroxy-2-(2-methoxy-propyl)-6,7-benzomorphan hydrobromide (MRZ 2549) had no effect on the levels of this hormone. Pretreatment with the highly selective mu-antagonist beta-funaltrexamine (beta-FNA), the fumarate methyl ester derivative of naltrexone, blocked the actions of both mu-agonists and MR 2034, indicating that opiate suppression of LH secretion is mediated by mu-receptors. This was further confirmed by in-vitro studies: the KCl-induced release of LHRH from perifused hypothalami obtained from ovariectomized rats was significantly reduced by DAGO but not by MRZ 2549. Prolactin secretion was stimulated in a dose-dependent manner by both mu- and kappa-agonists. The stimulation caused by morphine and DAGO was antagonized by beta-FNA, whereas that caused by the kappa-agonists MR 2034 and MZR 2549 was resistant to blockade by beta-FNA but not by naloxone (an antagonist which blocks all classes of opiate receptors when given in high doses). Thus prolactin secretion seems to be regulated by both mu- and kappa-opiate receptors, whereas the effects on LH secretion seem to involve mu-receptors only.
Pfeiffer
D G
DG
Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie, Martinsried, Federal Republic of Germany.
Pfeiffer
A
A
Almeida
O F
OF
Herz
A
A
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D009019:Morphinans / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010052:Ovariectomy; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D011388:Prolactin; D007986:Luteinizing Hormone