Evidence for the presence of 5-HT1-like receptors in rabbit isolated basilar arteries.
The 5-hydroxytryptamine (5-HT) receptor mediating contraction of rabbit isolated endothelium denuded basilar artery has been investigated. 5-HT and a variety of 5-HT receptor agonists contracted rabbit isolated basilar artery with a rank order of agonist potency: 5-carboxamidotryptamine (5-CT) greater than 5-HT greater than GR43175. None of these agonists relaxed rabbit isolated basilar artery when tone was elevated with prostaglandin F2alpha. The contractile response to both 5-HT and GR43175 was resistant to antagonism by GR38032, phentolamine, (+/-)-cyanopindolol and yohimbine. Ketanserin (100 nM) and mesulergine (100 nM) produced small significant rightward shifts of C-E curves to 5-HT with respective concentration-ratio shifts of 5.7 (1.5-21.0 95% confidence interval and 2.89 (1.1-7.6 95% confidence interval). GR43175-induced contraction was resistant to antagonism by ketanserin however the maximum response to GR43175 was significantly reduced in the presence of mesulergine, with no change in EC50. Methiothepin was a potent antagonist of the contractile actions of both 5-HT and GR43175, with respective pA2 values against each agonist of 10.3 and 9.9. The slope of the Schild regression for methiothepin against 5-HT-induced contraction was significantly less than unity. Methiothepin (100 nM) had no effect on the contractile response to the thromboxane A2 mimetic U-46619. It is concluded that 5-HT and GR43175 contract rabbit isolated basilar artery by activating a 5-HT1-like receptor. In addition 5-HT may activate a population of 5-HT2 receptors producing a further contraction of rabbit isolated basilar artery.(ABSTRACT TRUNCATED AT 250 WORDS)
Parsons
A A
AA
Department of Physiological Sciences, University of Manchester, U.K.
Whalley
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ET
D000818:Animals; D001488:Basilar Artery / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D012701:Serotonin; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D015237:Dinoprost