PRESYNAPTIC INHIBITORY ACTION OF 5-HYDROXYTRYPTAMINE IN DOG ISOLATED SAPHENOUS-VEIN

The effect of 5‐hydroxytryptamine on contractile responses to sympathetic nerve stimulation has been studied in the dog isolated saphenous vein. Electrical stimulation (0.1 to 10 Hz) of dog saphenous vein strips produced frequency‐dependent contractions. Contractions produced by stimulation at 2 Hz were almost completely blocked by tetrodotoxin (3.1 × 10−8 mol/l) or phentolamine (5.0 × 10−6 mol/l) but mecamylamine (5.0 × 10−6 mol/l) had little effect. This suggests that the contractions were mediated predominantly through noradrenaline release from postganglionic noradrenergic nerves. Contractions produced by intermittent electrical stimulation at 2 Hz were inhibited by 5‐hydroxytryptamine (1.0 × 10−9 to 1.0 × 10−7 mol/l) in a concentration‐dependent manner whilst contractions induced by exogenous noradrenaline were not affected. The inhibitory action of 5‐hydroxytryptamine was most marked at low frequencies of stimulation and with low pulse numbers. High external calcium concentrations (3.9 and 5.2 × 10−3 mol/l) reduced the inhibitory action of 5‐hydroxytryptamine. Cyproheptadine (1.0 × 10−8 mol/l to 1.0 × 10−6 mol/l) or morphine (1.0 × 10−7 mol/l to 1.0 × 10−5 mol/l) did not antagonize the inhibitory action of 5‐hydroxytryptamine. Methysergide (1.0 × 10−7 mol/l) slightly reduced the contractions produced by electrical stimulation and only weakly antagonized the action of 5‐hydroxytryptamine. It is suggested that a 5‐hydroxytryptamine receptor exists presynaptically in the dog isolated saphenous vein strip and that stimulation of this receptor by low concentrations of 5‐hydroxytryptamine inhibits the release of noradrenaline from noradrenergic nerves. This receptor type is resistant to blockade by ‘classical’ 5‐hydroxytryptamine antagonists. 1979 British Pharmacological Society