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Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1D receptor antagonist.

Abstract：

:1. It has previously been shown that the antimigraine drug, sumatriptan, a putative 5-HT1D receptor agonist, decreases porcine common carotid and arteriovenous anastomotic blood flows, but slightly increases the arteriolar (capillary) blood flow to the skin and ears. Interestingly, such responses, being mediated by 5-HT1-like receptors, are resistant to blockade by metergoline, which, in addition to displaying a very high affinity for (and occasionally intrinsic efficacy at) the 5-HT1D receptor subtypes, blocks (with lower potency than methiothepin) some 5-HT1D receptor-mediated vascular responses. These findings raise doubts whether sumatriptan-sensitive 5-HT1-like receptors mediating changes in the distribution of porcine carotid blood flow are identical to cloned 5-HT1D receptors. With the recent advent of the potent and selective 5-HT1D receptor antagonist, GR127935, we have examined in the present study whether the carotid vascular effects of sumatriptan in the pig are amenable to blockade by GR127935. 2. In animals pretreated with saline, sumatriptan (30, 100 and 300 micrograms kg-1, i.v.) reduced the total carotid and arteriovenous anastomotic blood flows in a dose dependent manner. In contrast, sumatriptan increased blood flow to the skin, ears and fat, although the total capillary fraction was not significantly affected. 3. While GR127935 pretreatment (0.25 and 0.5 mg kg-1) itself slightly reduced the total carotid and arteriovenous anastomotic blood flows, carotid vasoconstrictor responses to sumatriptan were either partly (0.25 mg kg-1) or completely (0.5 mg kg-1) blocked by the compound. In GR127935 pretreated animals, the sumatriptan-induced increases in blood flow to the skin, ears and fat were also attenuated. 4. Taken together, the results suggest that arteriovenous anastomotic constriction and, possibly, arteriolar dilatation in the skin, ears and fat by sumatriptan are mediated by 5-HT1D receptors. Therefore, vascular 5-HT1-like receptors in the porcine carotid bed appear to be identical to 5-HT1D receptors.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

De Vries P,Heiligers JP,Villalón CM,Saxena PR

doi

10.1111/j.1476-5381.1996.tb15370.x

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

85-92

issue

eissn

0007-1188

issn

1476-5381

journal_volume

118

pub_type

杂志文章

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Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1D receptor antagonist.