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

Abstract

The effects of noradrenaline uptake inhibitors on contractions evoked by electric field stimulation, noradrenaline, clonidine, 5-hydroxytryptamine, ATP, high K +, and BaCl 2 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 (3×10 −8–3×10 −5 M) and the inhibitory effect of protriptyline was reversible, while xylamine produced long-lasting inhibition. All three noradrenaline uptake blockers inhibited the clonidine (3×10 −6 M) or 5-hydroxytryptamine (10 −5 M)-induced contraction. Protriptyline and amitriptyline at concentrations of 3×10 −6–3×10 −5 M reversibly inhibited the ATP (10 −4 M)-induced monophasic contraction. In contrast, xylamine ((1–3)×10 −5 M) had no effect. Protriptyline and amitriptyline but not xylamine concentration-dependently reduced the high K + (6×10 −2 M)-induced sustained contraction with respective IC 50 values of 1.81×10 −6 M and 8.6×10 −7 M. Protriptyline and amitriptyline at 10 −5 M reversibly inhibited BaCl 2 (3×10 −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.