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.
Tiligada
E
E
Department of Pharmacology and Therpeutics, University of Wales College of Medicine, Heath Park, U.K.
Wilson
J F
JF
D000818:Animals; D004873:Ergolines / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology; D000521:alpha-MSH / Q000378:metabolism*
D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D000521:alpha-MSH; D013469:Sulpiride; D011188:Potassium