D2-but not D1-dopamine receptors are involved in the inhibitory control of alpha-melanocyte-stimulating hormone release from the rat hypothalamus

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Abstract
Release of alpha-melanocyte-stimulating hormone (α-MSH) from slices of rat hypothalamus superfused with artificial cerebro-spinal fluid (ACSF) was quantified by radioimmunoassay. Addition of 10-6 M quinpirole, a D2-dopamine receptor agonist, to the superfusion medium caused a significant (P < 0.001) reduction in the amount of α-MSH released upon depolarisation with 50 mM potassium from 319 ±37% to 110 ±16% of basal release in normal ACSF (mean ±S.E.M.). Basal peptide release in the presence of quinpirole was unaffected. Sulpiride, a D2-dopamine receptor antagonist, at a concentration of 10-6 M, induced a significant (P < 0.05) increase of both basal and potassium-stimulated α-MSH release to 203 ±21% and 447 ±88% of basal release in normal ACSF respectively. The latter increases were abolished when sulpiride and quinpirole were added in combination. SK&F 38393-A and SCH 23390, a D1-dopamine agonist and antagonist respectively, had no significant effect on either basal or potassiumstimulated α-MSH release. It is proposed that endogenous dopamine exerts an inhibitory control on α-MSH release from the rat hypothalamus via D2-dopamine receptors and that in isolated hypothalamic slices there is a tonic inhibition of peptide release due to the activity of this system.