Kappa-opioid-receptor-mediated regulation of alpha-melanocyte-stimulating hormone secretion and tuberohypophyseal dopaminergic neuronal activity.
The effects of the kappa-opioid receptor agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene- acetamide methanesulfonate hydrate (U-50488) were examined on alpha-melanocyte-stimulating hormone (alpha-MSH) secretion and the activity of tuberohypophysial dopamine (DA) neurons in the male rat. Tuberohypophysial DA neuronal activity was estimated by measuring: (1) the rate of DA synthesis [accumulation of 3,4-dihydroxyphenylalanine (DOPA) following inhibition of aromatic L-amino acid decarboxylase], and (2) DA metabolism [concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC)] in the intermediate lobe of the pituitary. U-50488 produced a dose- and time-dependent increase in plasma concentrations of alpha-MSH which was accompanied by a decrease in the accumulation of DOPA and in the intermediate lobe. The effects of U-50488 were blocked by pretreatment with the DA agonist apomorphine but not by the beta-adrenergic antagonist propranolol. The effects of U-50488 on plasma alpha-MSH concentrations and intermediate-lobe DOPA accumulation were blocked by pretreatment with the selective kappa-opioid receptor antagonist nor-binaltorphimine. These results indicate that U-50488, by acting on kappa-opioid receptors, inhibits the activity of intermediate-lobe tuberohypophysial DA neurons, and through this action increases the secretion of alpha-MSH from melanotrophs.
Manzanares
J
J
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
Lookingland
K J
KJ
Moore
K E
KE
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D000521:alpha-MSH / Q000032:analysis / Q000378:metabolism*
D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D015102:3,4-Dihydroxyphenylacetic Acid; D000521:alpha-MSH; D004295:Dihydroxyphenylalanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D011433:Propranolol; D001058:Apomorphine; D004298:Dopamine