5-HT1-LIKE RECEPTORS MEDIATE CONTRACTIONS OF THE RABBIT SAPHENOUS-VEIN

5-Hydroxytryptamine (5-HT) elicited concentration-dependent contractions of the rabbit isolated saphenous vein. The effects of 5-HT were mimicked by 5-carboxamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969) and sumatriptan; the rank order of potency (pD2 values) was 5-CT (7.6) > 5-HT (6.9) > 9-OH-DPAT (6.2) > RU 24969 (6.1) > sumatriptan (5.7). The maximal response to RU 24969 was less than that to the other compounds, implying that RU 24969 may behave as a partial agonist. Methiothepin (10(-8), 3 . 10(-8) and 3 . 10(-7) M), ketanserin (10(-7), 3 . 10(-7) and 10(-6) M) and spiperone (10(-7), 10(-6) and 10(-5) M), but not 1-alpha-H,3-alpha,5-alpha-H-tropan-3-yl-3,5-dichlorobenzoate (MDL 7222; 10(-7), 10(-6) or 10(-6) M), cyanopindolol (10(-7) and 10(-6) M) or propranolol (10(-7) and 10(-6) M), shifted the concentration-effect curve of 5-HT to the right in a concentration-dependent manner with pA2 values of 8.25, 7.51 and 6.12, respectively. The high activity of 5-CT and methiothepin compared to, respectively, 5-HT and ketanserin (and spiperone) suggests that the contraction of the rabbit saphenous vein is not mediated by 5-HT2 receptors. The receptor involved seems to be mainly 5-HT1-like, similar to the one mediating contraction of the dog saphenous vein, human basilar artery and porcine cranial arteriovenous anastomoses.