PREJUNCTIONALLY MEDIATED INHIBITION OF NEUROTRANSMISSION BY ISOPRENALINE IN RAT VAS-DEFERENS

Effects of isoprenaline on monophasic contractions evoked by electric field stimulation were studied in rat isolated prostatic vas deferens. Isoprenaline reduced electrically evoked contractions (EC50: 0.27 +/- 0.05 mu M), and propranolol concentration-dependently antagonized the effect of isoprenaline. In contrast, isoprenaline (0.3-3 mu M) did no t affect the contractile response induced by exogenous noradrenaline o r ATP, while forskolin (100 nM) attenuated agonist-induced contraction . In some tissues, adrenergic and purinergic components of the electri cally evoked contraction were isolated by exposure to alpha,beta-methy lene ATP (3 mu M) and prazosin (3 mu M), respectively. Isoprenaline in duced a greater inhibition of purinergic than adrenergic component of the electrically evoked contraction. Iberiotoxin (50 nM), glibenclamid e (3 mu M), 4-aminopyridine (0.3 mM) and tetraethylammonium ions (1 mM ) attenuated the effect of isoprenaline. These results indicate that i soprenaline-induced inhibition of the electrically evoked (both purine rgic and adrenergic) contraction was mediated primarily through activa tion of prejunctional beta-adrenoceptors, which probably inhibited rel ease of contractile transmitters from sympathetic nerves supplying vas deferens. Lack of effect of isoprenaline on agonist-induced contracti on does not favour a functional role of beta-adrenoceptors in vas smoo th muscle.