Vasoconstrictor 5-HT receptors in the smooth muscle of the rat middle cerebral artery

Serotonin (5-HT) can constrict cerebral arteries via activation of 5-HT1B and 5-HT2A receptors. Our goal was to reveal the importance and relative contribution of the two 5-HT receptor subtypes to the serotonin-induced vasoconstriction in the rat middle cerebral artery. The vasoconstrictor effects of 5-carboxamidotryptamine, sumatriptan and 5-HT were measured without and with pre-treatment with SB 216641 (5-HT1B antagonist), or ritanserin, (5-HT2A antagonist), in endothelium-denuded arteries, in vitro. All agonists caused vasoconstrictions. The order of potency (EC50) of the compounds was: 5-carboxamidotryptamine (14±3 nM)>5-HT (270±30 nM)>sumatriptan (5.8±1.9 μM). The concentration-response curve of 5-carboxamidotryptamine resembled the sum of two sigmoid curves (EC50 14±3 nM and 15±7 μM), and SB 216641 and ritanserin antagonized its low and high concentration components, respectively. Vasoconstrictions evoked by 5-HT at low and high concentrations were also fully antagonized by SB 216641 and ritanserin, respectively. Sumatriptan constricted the middle cerebral artery exclusively via 5-HT1B receptors. The efficacy of 5-carboxamidotryptamine and sumatriptan was low in comparison to the maximum contractile force elicited by 120 mmol/l KCl, reaching only 18-23% for 5-HT1B and 14% for 5-HT2A receptor activation. In conclusion, 5-HT produced small vasoconstrictions in the rat middle cerebral artery that were mediated by 5-HT1B receptors with high potency and by 5-HT2A receptors with low potency. Thus, 5-HT may have a minor physiological role in blood flow regulation via 5-HT1B receptor activation while 5-HT2A receptors seem to have a pathophysiological role in this vessel.