Hester R K, Weiss G B, Fry W J
J Pharmacol Exp Ther. 1978 Nov;207(2):364-71.
The action and interactions of three vasoconstrictors, norepinephrine (NE), dopamine (DA) and elevated potassium ion (K+) on contractile responses and associated 45Ca movements were investigated in isolated rabbit and canine renal arteries (RA). Dose-response curves indicate that NE is 39 times more potent than DA in canine RA and 122 times more potent in rabbit RA. Prior exposure to 80 mM K+ did not prevent contractile responses to NE or DA but, conversely, K+ -induced responses did not occur after exposure to NE or DA. Responses to NE persisted after maximum DA-induced contractions but only a small response to DA was observed after a maximum NE-induced contraction. After 30 to 60 min in either a O-Ca or a O-Ca plus 0.05 mM EDTA solution, contractile responses were differentially inhibited (K+ more than DA more than NE). Efflux of 45Ca into a O-Ca plus EDTA solution was qualitatively similar in canine and rabbit RA. Addition of K+, DA or NE decreased the rate of 45Ca efflux in both RA; phentolamine abolished the NE-induced decrease and had no effect on the K+-induced decrease. The observed decrease in 45Ca efflux may reflect an inward shift of 45Ca from membrane binding sites. The mechanisms by which this effect is obtained appear to differ for K+, DA and NE. The differing actions of NE and DA cannot be explained solely by variations in potency at a singel type of receptor.
研究了三种血管收缩剂,即去甲肾上腺素(NE)、多巴胺(DA)和高钾离子(K+)对离体兔和犬肾动脉(RA)收缩反应及相关45Ca转运的作用和相互作用。剂量反应曲线表明,在犬肾动脉中,NE的效力比DA高39倍,在兔肾动脉中高122倍。预先暴露于80 mM K+并不妨碍对NE或DA的收缩反应,但相反,在暴露于NE或DA后不会出现K+诱导的反应。在最大DA诱导的收缩后,对NE的反应持续存在,但在最大NE诱导的收缩后,仅观察到对DA的小反应。在O-Ca或O-Ca加0.05 mM EDTA溶液中孵育30至60分钟后,收缩反应受到不同程度的抑制(K+>DA>NE)。犬和兔肾动脉中45Ca向O-Ca加EDTA溶液的流出在性质上相似。添加K+、DA或NE均降低了两种肾动脉中45Ca的流出速率;酚妥拉明消除了NE诱导的降低,对K+诱导的降低无影响。观察到的45Ca流出减少可能反映了45Ca从膜结合位点向内的转移。获得这种效应的机制似乎因K+、DA和NE而异。NE和DA的不同作用不能仅通过单一类型受体上效力的差异来解释。