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)