Wilke R A, Hsu S F, Jackson M B
Department of Internal Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53706, USA.
J Pharmacol Exp Ther. 1998 Feb;284(2):542-8.
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 (IK) 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 IK under voltage clamp. This effect is concentration-dependent, with a maximal inhibition of 40 +/- 5% and an EC50 of 1.8 +/- 1.0 microM. It can be blocked with either a nonselective D2-like antagonist (100 microM eticlopride) or with the highly selective D4 antagonist, RBI-257 (10 microM). 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 IK in this preparation. Kinetic analysis demonstrated that the amplitude of both the rapidly and slowly inactivating phases of neurohypophysial IK 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.
多巴胺在体内影响神经垂体肽的释放。然而，这种作用在多大程度上是由神经垂体内直接的多巴胺能作用引起的仍不清楚。通过对大鼠垂体后叶薄片使用膜片钳技术，我们现在提供证据表明多巴胺能激动剂抑制神经垂体神经末梢的钾电流（IK）。在电压钳制下，用多巴胺受体激动剂（±）-2-（N-苯乙基-N-丙基）-氨基-5-羟基四氢萘（PPHT）进行灌流，可引起全终末IK的可逆性抑制。这种作用呈浓度依赖性，最大抑制率为40±5%，半数有效浓度（EC50）为1.8±1.0微摩尔。它可被非选择性D2样拮抗剂（100微摩尔的依托必利）或高选择性D4拮抗剂RBI-257（10微摩尔）阻断。U101958（RBI-257的衍生物）表现出与PPHT相似的激动剂活性。在该制剂中，SKF 38393（一种D1/D5激动剂）和喹吡罗（一种D2/D3激动剂）对全终末IK均无任何作用。动力学分析表明，神经垂体IK快速和缓慢失活阶段的幅度均因D4受体激活而降低。此前已表明这两个独立的电流成分分别代表通过两种不同钾通道的电流，即A电流通道和高电导Ca++激活的K+通道。因此，这两种通道类型均可被D4受体调节。这种作用可能会增强体内神经垂体肽的释放。
