Pharmacological identification of ¦Á₁- and ¦Á₂-adrenoceptor subtypes involved in the vasopressor responses induced by ergotamine in pithed rats

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• 作者：Ma. Trinidad Villamil-Hern¨¢ndez ; Oscar Alc¨¢ntara-V¨¢zquez ; Araceli S¨¢nchez-L¨®pez ; David Centuri¨®n
• 关键词：¦Á1-adrenoceptor ; ¦Á2-adrenoceptor ; Ergotamine ; Migraine
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：5 September, 2013
• 年：2013
• 卷：715
• 期：1-3
• 页码：262-269
• 全文大小：494 K

文摘

Ergotamine has been used in clinical practice for the acute treatment of migraine for over 90 years. So far, it is known that ergotamine interacts with diverse receptors (including ¦Á_1/2-adrenoceptors, 5-HT₁, 5-HT₂ and D₂-like receptors) and that produces increases in mean blood pressure which are significantly blocked by yohimbine, a classical ¦Á₂-adrenoceptor antagonist with a moderate affinity for ¦Á₁-adrenoceptors. Since ¦Á_1/2-adrenoceptors mediate vasopressor and vasoconstrictor responses in the cardiovascular system, this study was designed to identify the ¦Á-adrenoceptor subtypes (¦Á_1A, ¦Á_1B, ¦Á_1D, ¦Á_2A, ¦Á_2B and ¦Á_2C) involved in ergotamine-induced vasopressor responses in pithed rats. In male Wistar pithed rats baseline heart rate and blood pressure were recorded. Then, the vasopressor responses to intravenous (i.v.) bolus injections of ergotamine were determined after administration of vehicle or several ¦Á_1?2-adrenoceptor antagonists. I.v. administration of the antagonists prazosin (¦Á₁, 0.1-30 ¦Ìg/kg), rauwolscine (¦Á₂, 0.3-300 ¦Ìg/kg), prazosin (0.1 ¦Ìg/kg) plus rauwolscine (0.3 ¦Ìg/kg), 5-methylurapidil (¦Á_1A, 100 and 300 ¦Ìg/kg), L-765,314 (¦Á_1B, 100 and 300 ¦Ìg/kg), BMY 7378 (¦Á_1D, 100 and 300 ¦Ìg/kg), BRL44408 (¦Á_2A, 300 and 1000 ¦Ìg/kg) and JP-1302 (¦Á_2C, 300 ¦Ìg/kg), significantly blocked the vasopressor responses to ergotamine, whereas imiloxan (¦Á_2B, 1000 and 3000 ¦Ìg/kg), JP-1302 (100 ¦Ìg/kg) or the corresponding vehicles (saline 0.9 % , propylene glycol 20 % or dimethyl sulfoxide 10 % ; 1 ml/kg) failed to modify the responses to ergotamine. The above results suggest that the vasopressor responses to ergotamine in pithed rats are mainly mediated by ¦Á_1A-, ¦Á_1B-, ¦Á_1D-, ¦Á_2A- and ¦Á_2C-adrenoceptors and may explain its adverse/therapeutic effects.