The 5-HT1B/1D receptor agonist sumatriptan is effective in aborting acute attacks of migraine and is known to cause constriction of cranial arteries as well as some peripheral blood vessels. The present study set out to investigate whether 5-HT1B and/or 5-HT1D receptors mediate contractions of the human isolated middle meningeal and temporal arteries (models for anti-migraine efficacy) and coronary artery and saphenous vein (models for side-effect potential). Concentration-response curves were made with sumatriptan (1 nM-100 μM) in blood vessels in the absence or presence of selective antagonists at 5-HT1B (SB224289) and 5-HT1D (BRL15572) receptors. SB224289 antagonized sumatriptan-induced contractions in all blood vessels, although the antagonism profile was different amongst these blood vessels. In the temporal artery, SB224289 abolished contraction to sumatriptan, whereas in the middle meningeal artery and saphenous vein sumatriptan-induced contractions were blocked in an insurmountable fashion. Moreover, SB224289 acted as a weak surmountable antagonist in the coronary artery (pKB: 6.4±0.2). In contrast, BRL15572 had little or no effect on sumatriptan-induced contractions in the four blood vessels investigated. In situ hybridization revealed the expression of 5-HT1B receptor mRNA in the smooth muscle as well as endothelial cells of the blood vessels, whereas the mRNA for the 5-HT1D receptor was only very weakly expressed. These results show that the 5-HT1B receptor is primarily involved in sumatriptan-induced contractions of human cranial as well as peripheral blood vessels.

5-HT receptors, BRL15572, Coronary artery, Cranial arteries, Human, Migraine, Saphenous vein, SB224289, Sumatriptan
dx.doi.org/10.1046/j.1468-2982.2002.00295.x, hdl.handle.net/1765/66752
Cephalalgia: an international journal of headache
Department of Pharmacology

van den Broek, R.W.M, Bhalla, P.L, Maassen van den Brink, A, de Vries, R.R.P, Sharma, H.S, & Saxena, P.R. (2002). Characterization of sumatriptan-induced contractions in human isolated blood vessels using selective 5-HT1B and 5-HT1D receptor antagonists and in situ hybridization. Cephalalgia: an international journal of headache, 22(2), 83–93. doi:10.1046/j.1468-2982.2002.00295.x