Memo M, Pizzi M, Belloni M, Benarese M, Spano P
Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, Italy.
J Neurochem. 1992 Nov;59(5):1829-35. doi: 10.1111/j.1471-4159.1992.tb11016.x.
3,4-Dihydroxyphenylethylamine (dopamine) D2 receptor agonists, including BHT 920 and bromocriptine, and the potassium channel opener minoxidil share the property of hyperpolarizing the plasma membrane by activating voltage-dependent potassium channels. These drugs were tested for their ability to inhibit the cyclic AMP formation induced by forskolin either in intact or in broken pituitary cells. In contrast to bromocriptine, which was active in both experimental systems, BHT 920 and minoxidil inhibited the forskolin-induced cyclic AMP formation in intact-cell but not in broken-cell preparations. The effects of BHT 920 were (a) concentration dependent, with a calculated IC50 of 0.7 microM, (b) dopaminergic in nature, being specifically antagonized by sulpiride, (c) not additive with those induced by minoxidil, and (d) less effective in the presence of potassium channel blockers, such as 4-aminopyridine and tetraethylammonium. These data indicate that the inhibition of forskolin-induced cyclic AMP formation by BHT 920 in intact pituitary cells is not a primary consequence of receptor occupation, but a late event, possibly related to the opening of voltage-dependent potassium channels elicited by this drug through the activation of a subtype of dopamine D2 receptors uncoupled to adenylyl cyclase.
3,4-二羟基苯乙胺（多巴胺）D2受体激动剂，包括BHT 920和溴隐亭，以及钾通道开放剂米诺地尔，都具有通过激活电压依赖性钾通道使质膜超极化的特性。对这些药物抑制福斯高林在完整或破碎的垂体细胞中诱导的环磷酸腺苷（cAMP）形成的能力进行了测试。与在两种实验系统中均有活性的溴隐亭不同，BHT 920和米诺地尔在完整细胞中而非破碎细胞制剂中抑制福斯高林诱导的cAMP形成。BHT 920的作用为：（a）浓度依赖性，计算得出的半数抑制浓度（IC50）为0.7微摩尔；（b）本质上为多巴胺能性，可被舒必利特异性拮抗；（c）与米诺地尔诱导的作用无相加性；（d）在钾通道阻滞剂（如4-氨基吡啶和四乙铵）存在时效果较差。这些数据表明，BHT 920在完整垂体细胞中抑制福斯高林诱导的cAMP形成并非受体占据的主要结果，而是一个后期事件，可能与该药物通过激活一种与腺苷酸环化酶解偶联的多巴胺D2受体亚型引发电压依赖性钾通道开放有关。
