5-HT RECEPTORS MEDIATING CONTRACTIONS OF THE ISOLATED HUMAN CORONARY-ARTERY

We investigated contractile responses of the isolated human coronary a rtery to 5-hydroxytryptamine (5-HT), washed human platelets, sumatript an and ergotamine. 5-HT (pD2: 6.8 +/- 0.1, E(max): 47.7 +/- 6.8 mN) an d platelets (effect 14.4 +/- 2.8 mN with 3.10(10) platelets/l) caused contractile responses which were attenuated by ketanserin (1 muM). In the presence of ketanserin (1 muM), both rauwolscine (1 and 10 muM) an d cyanopindolol (1 and 10 muM) caused concentration-dependent addition al antagonism against contractions induced by low (less-than-or-equal- to 1 muM) concentrations of 5-HT. Sumatriptan-induced contractions (pD 2: 6.2 +/- 0.1; E(max): 10.7 +/- 2.4 mN) were antagonized to a similar extent by both rauwolscine (1 muM) and cyanopindolol (1 muM) (pK(B): 6.5 +/- 0.1 and 6.4 +/- 0.1, respectively) and also by metergoline (0. 1 muM; pK(B): 7.2 +/- 0.1). The order of potency of antagonists agains t sumatriptan resembles the order reported for the human saphenous vei n 5-HT1D-like receptor. No significant additional antagonism by cyanop indolol (1 muM) or rauwolscine (1 muM) against platelet-induced contra ctile responses was observed. Ergotamine caused potent contractile res ponses (pD2: 8.4 +/- 0.3, E(max): 19.4 +/- 2.4 mN). It is concluded th at although 5-HT2 receptors predominantly mediate 5-HT-induced contrac tions, the 5-HT1-like receptor seems to play a role in coronary vasosp asm caused by low concentrations of 5-HT.