Kappa-Opioid-Receptor-Mediated Regulation of α-Melanocyte-Stimulating Hormone Secretion and Tuberohypophysial Dopaminergic Neuronal Activity

Abstract

The effects of the ĸ-opioid receptor agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide methanesulfonate hydrate (U-50488) were examined on α-melanocyte-stimulating hormone (α-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 α-MSH which was accompanied by a decrease in the accumulation of DOPA and in the concentration of DOPAC in the intermediate lobe. The effects of U-50488 were blocked by pretreatment with the DA agonist apomorphine but not by the β-adrenergic antagonist pro-pranolol. The effects of U-50488 on plasma α-MSH concentrations and intermediate-lobe DOPA accumulation were blocked by pretreatment with the selective ĸ-opioid receptor antagonist norbinaltorphimine. These results indicate that U-50488, by acting on ĸ-opioid receptors, inhibits the activity of intermediate-lobe tuberohypophysial DA neurons, and through this action increases the secretion of α-MSH from melanotrophs.