Effects of endothelin-1 on postjunctionally-mediated purinergic and adrenergic components of rat vas deferens contractile responses

Abstract

The effects of endothelin-1 (ET-1) on electrically- or drug-induced contractile responses mediated by purinergic or adrenergic receptors were studied in isolated prostatic portion of rat vas deferens. ET-1 (0.01 nM to 30 nM) concentration-dependently increased the contractions evoked by electrical field stimulation (EFS, 0.3 msec, 30 V, 8 Hz, 300 pulses). In the presence of prazosin, ET-1 (3 nM) strongly enhanced the prazosin-resistant responses to EFS, while after desensitization of purinergic receptors induced by alpha,beta-methylene adenosine 5'-triphosphate (mATP) the peptide only tended to enhance the mATP-resistant component of the electrically-evoked contractions. ET-1 failed to change the nonpurinergic nonadrenergic responses to electrical stimulation revealing after simultaneous administration of prazosin and mATP. ET-1 concentration-dependently increased the contractile effects of exogenous ATP (30 microM). The effect of ET-1 (3 nM) was not changed after tetrodotoxin (TTX, 0.3 microM) and guanethidine (10 microM). In the presence of TTX and guanethidine ET-1 potentiated the contractile effects of low (0.01-1 microM) concentrations of noradrenaline (NA) and did not change the contractions induced by NA at concentrations higher than 3 microM. Therefore, ET-1 exerted a potentiating effect on the contractility of the prostatic portion of rat vas deferens via postjunctional mechanisms underlying mainly the purinergic and partly the adrenergic smooth muscle contractile responses.