Yohimbine antagonises 伪_1A- and 伪_1D-adrenoceptor mediated components in addition to the 伪_2A-adrenoceptor component to pressor responses in the pithed rat

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• 作者：James R. Docherty ; ^{docherty@rcsi.ie}
• 关键词：伪1A-adrenoceptor ; 伪1D-adrenoceptor ; 伪2-adrenoceptor ; 伪2A-adrenoceptor ; Pithed rat ; Vasopressor responses
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：15 March, 2012
• 卷：679
• 期：1-3
• 页码：90-94
• 文件大小：496 K

摘要

We have recently shown that responses to pressor nerve stimulation in the pithed rat are mediated by 伪_1A- and 伪_1D-adrenoceptors, with no evidence for 伪₂-adrenoceptor involvement, and that responses previously identified as 伪₂-adrenoceptor mediated are actually 伪_1D-adrenoceptor mediated. We have now re-examined the subtypes of 伪-adrenoceptor involved in pressor responses produced by exogenous agonists in the pithed rat preparation to confirm whether 伪₂-adrenoceptors are involved in these responses. The 伪₂-adrenoceptor and 伪_1D-adrenoceptor antagonist yohimbine (1 mg/kg) and the 伪_2A-adrenoceptor antagonist methoxy-idazoxan (5 mg/kg) significantly shifted, but the 伪_1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspir o[4.5]decane-7,9-dione dihydrochloride) (1 mg/kg) did not affect, the pressor potency of the 伪₂-adrenoceptor agonist xylazine. 伪₁-adrenoceptor antagonists showed low potency against pressor responses to xylazine. The pressor potency of the 伪₁-adrenoceptor agonist amidephrine was not affected by BMY 3778 (1 mg/kg) but significantly shifted by prazosin (0.01 mg/kg) and by yohimbine (1 mg/kg). In contrast, the pressor potency of phenylephrine was significantly shifted by both yohimbine and BMY 7378 (1 mg/kg), but to a greater extent by the 伪_1A-adrenoceptor antagonist RS 100329 (5-Methyl-3-[3-[3-[4-[2-(2,2,2,trifluroethoxy) phenyl]-1-piperazinyl]propyl]-2,4-(1H,3H)-pyrimidinedione] hydrochloride) (0.1 mg/kg). In conclusion, we have identified and separated 伪_1A-, 伪_1D- and 伪_2A-adrenoceptor antagonist actions of yohimbine against pressor responses. Pressor responses to exogenous agonists in the pithed rat involve both 伪_1A- and 伪_1D-adrenoceptors and in addition, 伪_2A-adrenoceptors.