5-HT receptors mediating contraction of the isolated human coronary artery
We investigated contractile responses of the isolated human coronary artery to 5-hydroxytryptamine (5-HT), washed human platelets, sumatriptan and ergotamine. 5-HT (pD2: 6.8 ± 0.1, Emax: 47.7 ± 6.8 mN) and platelets (effect 14.4 ± 2.8 mN with 3 · 1010 platelets/1) caused contractile responses which were attenuated by ketanserin (1 μM). In the presence of ketanserin (1 μM), both rauwolscine (1 and 10 μM) and cyanopindolol (1 and 10 μM) caused concentration-dependent additional antagonism against contractions induced by low (⩽ 1 μM) concentrations of 5-HT. Sumatriptan-induced contractions (pD2: 6.2 ± 0.1; Emax: 10.7 ± 2.4 mN) were antagonized to a similar extent by both rauwolscine (1 μM) and cyanopindolol (1 μM) (pKB: 6.5 ± 0.1 and 6.4 ± 0.1, respectively) and also by metergoline (0.1 μM; pKB: 7.2 ± 0.1). The order of potency of antagonists against sumatriptan resembles the order reported for the human saphenous vein 5-HT1D-like receptor. No significant additional antagonism by cyanopindolol (1 μM) or rauwolscine (1 μM) against platelet-induced contractile responses was observed. Ergotamine caused potent contractile responses (pD2: 8.4 ± 0.3, Emax: 19.4 ± 2.4 mN). It is concluded that although 5-HT2 receptors predominantly mediate 5-HT-induced contractions, the 5-HT1-like receptor seems to play a role in coronary vasospasm caused by low concentrations of 5-HT.
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