Pharmacological identification of alpha1- and alpha2-adrenoceptor subtypes involved in the vasopressor responses induced by ergotamine in pithed rats.

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Villamil-Hernandez MT, Alcantara-Vazquez O, Sanchez-Lopez A, Centurion D

Pharmacological identification of alpha1- and alpha2-adrenoceptor subtypes involved in the vasopressor responses induced by ergotamine in pithed rats.

Eur J Pharmacol. 2013 Sep 5;715(1-3):262-9. doi: 10.1016/j.ejphar.2013.05.011. Epub 2013 May 22.

PubMed ID

23707349 [ View in PubMed

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Abstract

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 alpha1/2-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 alpha2-adrenoceptor antagonist with a moderate affinity for alpha1-adrenoceptors. Since alpha1/2-adrenoceptors mediate vasopressor and vasoconstrictor responses in the cardiovascular system, this study was designed to identify the alpha-adrenoceptor subtypes (alpha1A, alpha1B, alpha1D, alpha2A, alpha2B and alpha2C) 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 alpha12-adrenoceptor antagonists. I.v. administration of the antagonists prazosin (alpha1, 0.1-30 microg/kg), rauwolscine (alpha2, 0.3-300 microg/kg), prazosin (0.1 microg/kg) plus rauwolscine (0.3 microg/kg), 5-methylurapidil (alpha1A, 100 and 300 microg/kg), L-765,314 (alpha1B, 100 and 300 microg/kg), BMY 7378 (alpha1D, 100 and 300 microg/kg), BRL44408 (alpha2A, 300 and 1000 microg/kg) and JP-1302 (alpha2C, 300 microg/kg), significantly blocked the vasopressor responses to ergotamine, whereas imiloxan (alpha2B, 1000 and 3000 microg/kg), JP-1302 (100 microg/kg) or the corresponding vehicles (saline 0.9%, propylene glycol 20% or dimethyl sulfoxide 10%; 1ml/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 alpha1A-, alpha1B-, alpha1D-, alpha2A- and alpha2C-adrenoceptors and may explain its adverse/therapeutic effects.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ergotamine	Alpha-2C adrenergic receptor	Protein	Humans	Unknown	Not Available	Details