OPPOSITE MODULATION OF NORADRENALINE AND ATP RELEASE IN GUINEA-PIG VAS-DEFERENS THROUGH PREJUNCTIONAL BETA-ADRENOCEPTORS - EVIDENCE FOR THEBETA(2) SUBTYPE

Activation of prejunctional beta-adrenoceptors has been suggested to i ncrease the release of noradrenaline but to decrease the neural releas e of ATP in the guinea-pig vas deferens. Experiments were carried out to determine the subtype of beta-adrenoceptor involved. In [H-3]-norad renaline-preincubated tissues superfused with medium containing prazos in and suramin, isoprenaline (1-100 nM), salbutamol (0.01-1 mu M) and terbutaline (0.1-10 mu M) increased the overflow of tritium but reduce d the overflow of ATP elicited by electrical stimulation (210 pulses/7 Hz). The effects of isoprenaline were blocked by the beta(2)-selectiv e antagonist 1-[2,3-(dihydro-7-methyl-1H-inden-4-yl) oxy]-3-[(1-methyl ethyl)amino]-2-butanol (ICI 118,551; 100 nM). In prazosin- and suramin -free medium, isoprenaline (100 nM) did not change the overflow of ATP elicited by exogenous noradrenaline (10 mu M). Isoprenaline (1-100 nM ), salbutamol (0.01-1 mu M) and terbutaline (0.1-10 mu M) reduced the initial twitch contraction elicited by electrical stimulation (210 pul ses/7 Hz) in prazosin- and suramin-free medium as well as the isolated purinergic neurogenic contraction obtained by exposure to prazosin. T hey increased or tended to increase the secondary sustained contractio n elicited by electrical stimulation in prazosin- and suramin-free med ium as well as the isolated adrenergic neurogenic contraction obtained in the presence of suramin. The inhibition by isoprenaline of the iso lated purinergic contraction was attenuated by ICI 118,551 (100 nM) bu t not by the beta(1)-selective antagonist 4-trifluoromethyl-2-imidazol yl)phenoxy]-2-propanol (CGP 20712A; 100 nM). The results confirm the o pposite beta-adrenoceptor-mediated modulation of noradrenaline and neu ral ATP release in the guinea-pig vas deferens. They show that the pre junctional beta-adrenoceptor is of the beta(2) subtype.