Dopamine inhibits the release of immunoreactive β-endorphin from rat hypothalamus in vitro

Abstract

Mediobasal hypothalamus tissue (MBH) from adult male rats was incubated in Krebs-Ringer bicarbonate medium (KRB). KRB was changed at 15 min intervals and the concentration of immunoreactive β-endorphin (β-ENDi) in the medium was measured by radioimmunoassay. Incubation of MBH tissue in normal KRB resulted in a constant release rate of β-ENDi of approximately 1% of the tissue content per h. KRB containing 45 mM K + causes a two fold increase in the release rate of β-ENDi which was Ca 2+ dependent. Dopamine (0.01–1.0 μM) inhibits both the spontaneous and the K +-stimulated release of β-ENDi in a dose related manner. The dopamine receptor blocking agent haloperidol prevents this inhibitory effect of dopamine. The selective D-1 receptor agonist SKF 38393 does not affect the release rate of β-ENDi; whereas the selective D-2 receptor agonist LY 141865 inhibits both the spontaneous and K +-stimulated release of β-ENDi. The effects of LY 141865 can be blocked by (−)-sulpiride, a selective D-2 receptor antagonist. Norepinephrine only weakly inhibits the K +-stimulated release of β-ENDi, and effect that can be blocked by haloperidol but not by the α-adrenoceptor blocker phentolamine. At concentrations tested (0.01–1.0 μM), isoproterenol, 5-hydroxytryptamine, carbachol and 8-Br-cAMP (1.0 μM) do not affect β-ENDi release. It is concluded that dopamine can inhibit the release of β-ENDi from hypothalamic neurons via a D-2 receptor mechanism.