OPPOSITE MODULATION OF COTRANSMITTER RELEASE IN GUINEA-PIG VAS-DEFERENS - INCREASE OF NORADRENALINE AND DECREASE OF ATP RELEASE BY ACTIVATION OF PREJUNCTIONAL BETA-ADRENOCEPTORS

Effects of isoprenaline on contraction, release of noradrenaline and r elease of ATP elicited by electrical field stimulation (210 pulses, 7 Hz) as well as on contractions elicited by exogenous noradrenaline and ATP were studied in the isolated vas deferens of the guinea pig. Rele ase of noradrenaline was assessed as overflow of total tritium after p reincubation with [H-3]-noradrenaline. ATP was measured by means of th e luciferin-luciferase technique. In [H-3]-noradrenaline-pretreated ti ssues, electrical stimulation elicited an overflow of tritium and ATP and a biphasic contraction. Isoprenaline (1-100 nM) reduced the contra ction, mainly phase I, and enhanced the evoked overflow of tritium; ev oked overflow of ATP was not changed significantly. No, or almost no, contraction remained in [H-3]-noradrenaline-pretreated tissues exposed to both prazosin (0.3 mu M) and suramin (300 mu M), and the evoked ov erflow of ATP was reduced by about 82%. Under these conditions, isopre naline (1-100 nM) again enhanced the evoked overflow of tritium, but i t now decreased the evoked overflow of ATP. Propranolol (1 mu M), when added on top of prazosin and suramin, prevented the effects of isopre naline (1-100 nM). In some tissues not pretreated with [H-3]-noradrena line, purinergic and adrenergic components of the neurogenic contracti on (again to 210 pulses, 7 Hz) were isolated by exposure to prazosin ( 0.3 mu M) and suramin (300 mu M), respectively. Isoprenaline (1-100 nM ) decreased the isolated purinergic component but did not change signi ficantly the isolated adrenergic component. Contractions elicited by A TP (1000 mu M) were not changed and contractions elicited by noradrena line (100 mu M) were slightly increased by isoprenaline (1-100 nM). Is oprenaline (100 nM) did not change the degradation of ATP (100 mu M) b y pieces of the vas deferens. It is concluded that, in the guinea-pig vas deferens, activation of prejunctional beta-adrenoceptors modulates the neural release of noradrenaline and ATP in opposite directions: r elease of noradrenaline is enhanced, whereas release of ATP is decreas ed.