Is the neuronal ATP release from guinea-pig vas deferens subject to alpha 2-adrenoceptor-mediated modulation?

Abstract

The effects of a variety of alpha 2-adrenoceptor agonists and antagonists were studied on stimulation-evoked release of endogenous ATP, measured by the luciferin-luciferase assay, and on the release of [3H]noradrenaline from the guinea-pig vas deferens. The biphasic mechanical contraction of the guinea-pig smooth muscle was recorded concomitantly. The alpha 2-adrenoceptor agonist, xylazine (1 microM) inhibited the field stimulation-evoked (8 Hz, 0.1 ms, 480 shocks) release of ATP and [3H]noradrenaline, and both phases of the contraction. The inhibitory effect of xylazine on the release of ATP, noradrenaline and muscle contraction was prevented by the selective alpha 2-adrenoceptor antagonist, CH 38083 [7,8-(methylenedioxi)-14 alpha-alloberbanol, 1 microM]. In the presence of prazosin (0.1-1 microM) or WB 4101 [2-(2,6-dimethoxyphenoxyethyl)aminomethyl- 1,4-benzodioxane hydrochloride, 0.1-1 microM], i.e. under the condition when the effect of noradrenaline on postjunctional alpha 1-adrenoceptors was excluded, the stimulation-evoked release of [3H]noradrenaline was significantly enhanced, however, the release of endogenous ATP and also both phases of contraction were reduced. In the presence of prazosin, xylazine was able to inhibit the stimulation-evoked release of ATP. In vas deferens dissected from reserpine pretreated (2 x 5 mg/kg, i.p.) guinea-pigs, the content of noradrenaline was 0.5% of control and there was no detectable evoked release of noradrenaline. Under this condition, the release of ATP evoked by electrical stimulation was still detectable, but the amount of ATP was much smaller than that measured from control animals. Xylazine did not reduce the release of ATP. Oxymetazoline, a relatively selective alpha 2-adrenoceptor agonist failed to inhibit the release of [3H]noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)