Inhibition of contractions by tricyclic antidepressants and xylamine in rat vas deferens

The effects of noradrenaline uptake inhibitors on contractions evoked by electric field stimulation, noradrenaline, clonidine, 5-hydroxytryptamine, ATP, high K⁺, and BaCl₂ in the epididymal half of rat isolated vas deferens were examined. Protriptyline, amitriptyline and xylamine concentration-dependently inhibited monophasic contractions induced by low frequency electrical stimulation (0.3 Hz, 1 ms duration, 60 V). Protriptyline and xylamine inhibited in a noncompetitive manner the contractile response induced by noradrenaline (3 x 10^-8-3 x 10^-5 M) and the inhibitory effect of protriptyline was reversible, while xylamine produced long-lasting inhibition. All three noradrenaline uptake blockers inhibited the clonidine (3 x 10^-6 M) or 5-hydroxytryptamine (10^-5 M)-induced contraction. Protriptyline and amitriptyline at concentrations of 3 x 10^-6-3 x 10^-5 M reversibly inhibited the ATP (10^-4 M)-induced monophasic contraction. In contrast, xylamine ((1-3) x 10^-5 M) had no effect. Protriptyline and amitriptyline but not xylamine concentration-dependently reduced the high K⁺ (6 x 10^-2 M)-induced sustained contraction with respective IC₅₀ values of 1.81 x 10^-6 M and 8.6 x 10^-7 M. Protriptyline and amitriptyline at 10^-5 M reversibly inhibited BaCl₂ (3 x 10^-3 M)-induced phasic contractions and xylamine (10^-5 M) had no effect. These findings demonstrate that tricyclic antidepressants might exert direct inhibitory action on mechanical contraction pathway, whilst xylamine, a structurally different inhibitor of noradrenaline uptake, may act mainly at α-adrenoceptors and other amine receptors on the smooth muscle of the rat vas deferens as a long-lasting nonselective antagonist, and it at least in part blocks sympathetic transmission.