Abstract

Dopamine influences the release of neurohypophysial peptides in vivo. However, the extent to which this effect is caused by a direct dopaminergic action within the neurohypophysis remains unclear. With use of the patch-clamp technique on thin slices of rat posterior pituitary glands, we now provide evidence that dopaminergic agonists inhibit potassium current (I_K) in neurohypophysial nerve terminals. Superfusion with the dopamine receptor agonist, (±)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin (PPHT), causes a reversible inhibition of whole-terminal I_Kunder voltage clamp. This effect is concentration-dependent, with a maximal inhibition of 40 ± 5% and an EC₅₀ of 1.8 ± 1.0 μM. It can be blocked with either a nonselective D₂-like antagonist (100 μM eticlopride) or with the highly selective D₄ antagonist, RBI-257 (10 μM). U101958 (a derivative of RBI-257) exhibits agonist activity similar to PPHT. Neither SKF 38393 (a D₁/D₅ agonist) nor quinpirole (a D₂/D₃ agonist) had any effect on whole-terminal I_K in this preparation. Kinetic analysis demonstrated that the amplitude of both the rapidly and slowly inactivating phases of neurohypophysialI_K are reduced by D₄ receptor activation. These two separate current components have previously been shown to represent current through two distinct potassium channels, an A-current channel and a high-conductance Ca⁺⁺-activated K⁺ channel. Thus, both channel types can be modulated by D₄ receptors. This effect is likely to enhance the release of neurohypophysial peptides in vivo.