Relative pre- and postjunctional roles of noradrenaline and adenosine 5'-triphosphate as neurotransmitters of the sympathetic nerves of guinea-pig and mouse vas deferens.

Experiments were designed to examine the relative roles of noradrenaline and adenosine 5'-triphosphate (ATP) as mediators of the contractile responses of the guinea-pig and the mouse vas deferens to electrical nerve stimulation. To study possible prejunctional actions of the agents used, in some experiments their effects on the secretion of [3H]noradrenaline were determined. The contractile responses were recorded with force displacement transducers. Pharmacological techniques were employed to examine the pre- and/or postjunctional effects mediated by noradrenaline and ATP, respectively. Noradrenaline-mediated components were "removed" by depleting the neuronal stores of noradrenaline (by pretreatment with reserpine), or by addition of adrenoceptor-blocking agents. ATP-mediated components were "removed" by desensitizing ATP receptors (with the stable analogue alpha, beta-methylene ATP). The results permit three major conclusions: (1) In both species noradrenaline and ATP "auto-inhibit" mechanisms responsible for transmitter secretion; the prejunctional effects of ATP are less marked in the mouse vas deferens, and in both species much weaker than those mediated by noradrenaline, acting via alpha 2-adrenoceptors. (2) In these species, both noradrenaline and ATP participate in the generation of both phases of the contractile responses to nerve stimulation. The relative roles of each vary with the frequency and train length of stimulation, and also with the species. The main transmitter of "phase I" contractions in guinea-pig vas deferens is ATP, and in the mouse vas deferens, noradrenaline. "Phase II" contractions are triggered mainly by noradrenaline, in both species. Sympathetic neuroeffector transmission in these tissues can be accounted for almost entirely in terms of dynamic interplay between pre- and postjunctional actions of noradrenaline and ATP. (3) The results are compatible with the hypothesis that ATP is a co-transmitter with noradrenaline in these sympathetic nerves.