Schwietert H R, Gouw M A, Wilhelm D, Wilffert B, van Zwieten P A
Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):463-71. doi: 10.1007/BF00169547.
The purpose of this investigation was to determine whether alpha 1-adrenoceptor subtypes (co)exist in the rat portal vein and, if so, whether they could be functionally associated with the phasic and tonic types of contraction as a response to alpha 1-adrenoceptor stimulation by phenylephrine. A low Ca2+ concentration (0.9 mmol/l) in the Tyrode solution enabled us to quantify changes both in the phasic myogenic activity and in the basal tone of the rat portal vein preparation very precisely. We used both competitive and non-competitive alpha-adrenoceptor antagonists which have been employed successfully by other investigators to discriminate between alpha 1-adrenoceptor subtypes in vascular and other tissues. Schild analysis showed that the competitive alpha-adrenoceptor antagonists prazosin, phentolamine, yohimbine, corynanthine, idazoxan, rauwolscine and 5-methyl-urapidil could not distinguish between the phasic and tonic responses to phenylephrine and/or different alpha 1-adrenoceptor subtypes in the rat portal vein. However, when we compared our pA2 values with those found to be representative indicators according to subclassifications based on the use of selective antagonists in different tissues, the alpha 1-adrenoceptors in the rat portal vein appeared to belong to the alpha 1L- or alpha 1a-subtype. This subclassification was not in accordance with the data obtained with the irreversible alpha-adrenoceptor antagonist chloroethylclonidine. However, the validity of this alkylating agent as a tool for receptor classification was restricted, at least in the rat portal vein, by its effects on receptor reserve.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是确定大鼠门静脉中是否存在α1 -肾上腺素能受体亚型（或共同存在），如果存在，它们是否能在功能上与去氧肾上腺素刺激α1 -肾上腺素能受体所引起的相位性和紧张性收缩类型相关。台氏液中低钙浓度（0.9 mmol/L）使我们能够非常精确地量化大鼠门静脉标本的相位性肌源性活动和基础张力的变化。我们使用了竞争性和非竞争性α -肾上腺素能受体拮抗剂，其他研究者已成功使用这些拮抗剂来区分血管和其他组织中的α1 -肾上腺素能受体亚型。希尔德分析表明，竞争性α -肾上腺素能受体拮抗剂哌唑嗪、酚妥拉明、育亨宾、柯楠因、咪唑克生、萝芙辛和5 -甲基-乌拉地尔无法区分大鼠门静脉对去氧肾上腺素的相位性和紧张性反应及/或不同的α1 -肾上腺素能受体亚型。然而，当我们将我们的pA2值与根据在不同组织中使用选择性拮抗剂进行的亚分类所发现的代表性指标进行比较时，大鼠门静脉中的α1 -肾上腺素能受体似乎属于α1L -或α1a -亚型。这种亚分类与用不可逆α -肾上腺素能受体拮抗剂氯乙可乐定获得的数据不一致。然而，至少在大鼠门静脉中，这种烷基化剂作为受体分类工具的有效性因其对受体储备的影响而受到限制。（摘要截短于250字）
