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

Release of alpha-melanocyte-stimulating hormone (alpha-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 less than 0.001) reduction in the amount of alpha-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 less than 0.05) increase of both basal and potassium-stimulated alpha-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 potassium-stimulated alpha-MSH release. It is proposed that endogenous dopamine exerts an inhibitory control on alpha-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.