5-HT_1B-receptors and vascular reactivity in human isolated blood vessels: Assessment of the potential craniovascular selectivity of sumatriptan

Aims: 5-HT_1B-receptor mediated vasoconstriction of cranial arteries is a potential mechanism by which 5-HT_1B/1D-receptor agonists such as sumatriptan produce their antimigraine effects. 5-HT_1B-receptors exist in other blood vessels which may give rise to unwanted vascular effects. Therefore we examined the distribution of 5-HT_1B-receptor immunoreactivity (i.r.) in human blood vessels (including target and nontarget vessels) and confirmed the functionality of this receptor protein, by comparing the vasoconstrictor effects of sumatriptan and 5-HT (the endogenous ligand) in isolated vessels. Methods: Blood vessels (middle meningeal, pial, temporal and uterine arteries and saphenous veins) were obtained from surgical patients (with consent). Sections of the vessels were prepared for routine immunohistochemical studies using specific 5-HT_1B- and 5-HT_1D-receptor antibodies. For functional studies, ring segments of the vessels were mounted in organ baths for isometric tension recording. Results: 5-HT_1B-receptor i.r. was detected on the smooth muscle layer in middle meningeal, pial and uterine arteries and in saphenous vein and sumatriptan produced contractions in these vessels with potency values (mean pEC₅₀) of 7.00, 7.08, 6.44 and 6.61, respectively, the magnitude of contraction was greatest in the cranial arteries with E_max values of 100.7, 60.3, 23.0 and 35.9%, respectively (expressed as a percentage of the reference agonist 45 mM KCl). 5-HT_1B-receptor i.r. was not detected in temporal artery and sumatriptan had no effect in this artery. 5-HT_1D-receptor i.r. was not detected in any of the vessels studied. Conclusions: Sumatriptan can evoke vasoconstriction in antimigraine target vessels and also in nontarget vessels through an action at 5-HT_1B-rcceptors. Sumatriptan acts preferentially to cause contraction in human cranial arteries compared with the other blood vessels we examined and this effect is likely to be shared by other drugs of this class.