Opposite modulation of cotransmitter release in guinea-pig vas deferens: increase of noradrenaline and decrease of...

Effects of isoprenaline on contraction, release of noradrenaline and release 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. Release of noradrenaline was assessed as overflow of total tritium after preincubation with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. In [3H]-noradrenaline-pretreated tissues, electrical stimulation elicited an overflow of tritium and ATP and a biphasic contraction. Isoprenaline (1-100 nM) reduced the contraction, mainly phase I, and enhanced the evoked overflow of tritium: evoked overflow of ATP was not changed significantly. No, or almost no, contraction remained in [3H]-noradrenaline-pretreated tissues exposed to both prazosin (0.3 microM) and suramin (300 microM), and the evoked overflow of ATP was reduced by about 82%. Under these conditions, isoprenaline (1-100 nM) again enhanced the evoked overflow of tritium, but it now decreased the evoked overflow of ATP. Propranolol (1 microM), when added on top of prazosin and suramin, prevented the effects of isoprenaline (1-100 nM). In some tissues not pretreated with [3H]-noradrenaline, purinergic and adrenergic components of the neurogenic contraction (again to 210 pulses, 7 Hz) were isolated by exposure to prazosin (0.3 microM) and suramin (300 microM), respectively. Isoprenaline (1-100 nM) decreased the isolated purinergic component but did not change significantly the isolated adrenergic component. Contractions elicited by ATP (1000 microM) were not changed and contractions elicited by noradrenaline (100 microM) were slightly increased by isoprenaline (1-100 nM). Isoprenaline (100 nM) did not change the degradation of ATP (100 microM) by 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: release of noradrenaline is enhanced, whereas release of ATP is decreased.