Cerebrovascular serotonergic receptors mediating vasoconstriction: further evidence for the existence of 5-HT2 receptors in rat and 5-HT1-like receptors in guinea-pig basilar arteries.

Pharmacological experiments were carried out on isolated basilar arteries (BA) from the brain vasculature of guinea-pig and rat in order to characterize post-junctional serotonergic receptors mediating contraction by the use of selective agonists and antagonists. The sensitivity to 5-HT was higher, but the intrinsic activity lower, in guinea-pig compared to rat vessels. The contractile potency of the 5-HT1 agonists, 5-carboxamidotryptamine (5-CT), was three times higher than 5-HT in guinea-pig but 16 times lower in rat BA. In arteries from both species the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), only caused weak contraction. In rat BA, where the serotonergic contractile receptors are ketanserin-sensitive, mesulergine inhibited the contraction in doses high enough to block 5-HT2 receptors, and also propranolol slightly inhibited the contraction, probably due to its binding to these receptors. Methiothepin, a potent antagonist of the 5-HT1-like receptors, affected the contraction in a non-competitive manner. The antagonist profile was different in guinea-pig BA: propranolol was ineffective, mesulergine caused a slight, non-surmountable inhibition, whereas methiothepin acted as a true, competitive antagonist. The data support previous suggestions that the serotonergic contraction in rat BA is mediated by 5-HT2 receptors, whereas the present data show that 5-HT1-like receptors predominate in guinea-pig BA.