d-布他拉莫对多巴胺诱导的离体兔肠系膜动脉舒张的立体特异性拮抗作用。

Stereospecific antagonism by d-butaclamol of dopamine-induced relaxation of the isolated rabbit mesenteric artery.

作者信息

Brodde O E, Freistühler J, Meyer F J

出版信息

J Cardiovasc Pharmacol. 1981 Jul-Aug;3(4):828-37. doi: 10.1097/00005344-198107000-00016.

DOI:10.1097/00005344-198107000-00016

Abstract

We characterized the properties of vascular dopamine receptors on isolated rabbit mesenteric arteries preincubated with phenoxybenzamine (10(-5) M) and contracted with prostaglandin F2 alpha (PGF2 alpha). The dose-response curve for dopamine-induced relaxation was shifted to the right by the dopamine receptor antagonist d-butaclamol (10(-7)--3 X 10(-6) M) in a concentration-dependent manner. The pA2 value for d-butaclamol was calculated as 6.77. In contrast, even a very high concentration (3 X 10(-6) M) of l-butaclamol had no effect, indicating that vascular dopamine receptors require stereospecificity of antagonists. In the same preparation the mechanism of relaxation by 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN; 3 X 10(-7)--10(-4) M) and bromocriptine (10(-6)--3 X 10(-4) M) was found to be dopaminomimetic, since only the dopamine receptor antagonists droperidol (10(-5) M) and metoclopramide (5 X 10(-5) M) could inhibit relaxations, whereas the beta-adrenoceptor antagonists pindolol (10(-7) M) and propranolol (10(-6) M) were without effect. It is concluded that receptors specific for dopamine exist on the rabbit mesenteric artery, which may tentatively be classified as belonging to the D1-type.

摘要

我们对预先用苯氧苄胺（10⁻⁵ M）孵育并被前列腺素F2α（PGF2α）收缩的离体兔肠系膜动脉上的血管多巴胺受体特性进行了表征。多巴胺受体拮抗剂d-布他拉莫（10⁻⁷ - 3×10⁻⁶ M）使多巴胺诱导的舒张剂量反应曲线以浓度依赖方式向右移动。计算出d-布他拉莫的pA2值为6.77。相比之下，即使是非常高浓度（3×10⁻⁶ M）的l-布他拉莫也没有作用，这表明血管多巴胺受体需要拮抗剂的立体特异性。在同一制剂中，发现2-氨基-6,7-二羟基-1,2,3,4-四氢萘（A-6,7-DTN；3×10⁻⁷ - 10⁻⁴ M）和溴隐亭（10⁻⁶ - 3×10⁻⁴ M）诱导舒张的机制是拟多巴胺能的，因为只有多巴胺受体拮抗剂氟哌利多（10⁻⁵ M）和甲氧氯普胺（5×10⁻⁵ M）能抑制舒张，而β-肾上腺素能受体拮抗剂吲哚洛尔（10⁻⁷ M）和普萘洛尔（10⁻⁶ M）则无作用。得出的结论是，兔肠系膜动脉上存在对多巴胺特异的受体，可初步归类为D1型。