Cerebrovascular serotonergic receptors mediating vasoconstriction: further evidence for the existence of 5‐HT2 receptors in rat and 5‐HTVIike receptors in guinea‐pig basilar arteries

Abstract

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 agonist, 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‐HT_1A 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.