Yohimbine antagonises ¦Á_1A- and ¦Á_1D-adrenoceptor mediated components in addition to the ¦Á_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：¦Á1A-adrenoceptor ; ¦Á1D-adrenoceptor ; ¦Á2-adrenoceptor ; ¦Á2A-adrenoceptor ; Pithed rat ; Vasopressor responses
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 出版时间：15 March, 2012
• 年：2012
• 卷：679
• 期：1-3
• 页码：90-94
• 全文大小：496 K

文摘

We have recently shown that responses to pressor nerve stimulation in the pithed rat are mediated by ¦Á_1A- and ¦Á_1D-adrenoceptors, with no evidence for ¦Á₂-adrenoceptor involvement, and that responses previously identified as ¦Á₂-adrenoceptor mediated are actually ¦Á_1D-adrenoceptor mediated. We have now re-examined the subtypes of ¦Á-adrenoceptor involved in pressor responses produced by exogenous agonists in the pithed rat preparation to confirm whether ¦Á₂-adrenoceptors are involved in these responses. The ¦Á₂-adrenoceptor and ¦Á_1D-adrenoceptor antagonist yohimbine (1 mg/kg) and the ¦Á_2A-adrenoceptor antagonist methoxy-idazoxan (5 mg/kg) significantly shifted, but the ¦Á_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 ¦Á₂-adrenoceptor agonist xylazine. ¦Á₁-adrenoceptor antagonists showed low potency against pressor responses to xylazine. The pressor potency of the ¦Á₁-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 ¦Á_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 ¦Á_1A-, ¦Á_1D- and ¦Á_2A-adrenoceptor antagonist actions of yohimbine against pressor responses. Pressor responses to exogenous agonists in the pithed rat involve both ¦Á_1A- and ¦Á_1D-adrenoceptors and in addition, ¦Á_2A-adrenoceptors.