Role of adenylate cyclase in modulatory effect of neuropeptide Y on [3H]noradrenaline release in guinea-pig vas deferens.

1. The effect of neuropeptide Y (NPY) on [3H]noradrenaline ([3H]NA) release-evoked by 5-Hz electrical stimulation or 5 microns calcium ionophore A23187 was studied in vitro in guinea-pig vas deferens. 2. The evoked tritium overflow (which reflected [3H]NA release) was determined by liquid scintillation spectrometry. 3. NPY, 1 microM, reduced electrically-evoked tritium overflow. NPY reduction was more pronounced upon 20-sec, 3 msec continuous stimulation (73.2 +/- 4.4%) and upon 5-min, 1 msec intermittent stimulation (47.8 +/- 2.4%) as compared to the reduction upon 5-min, 1 msec continuous stimulation (24.3 +/- 3.8%). Forskolin (0.1-1 microM) and theophylline (0.65-1.25 mM) dose-dependently diminished this NPY reducing effect. 4. NPY, 1 microM, reduced A23187-evoked tritium overflow by 52.3 +/- 7.1%. Forskolin (5 microM) and theophylline (1.25 mM) significantly decreased the effect of NPY. 5. It is concluded that in guinea-pig vas deferens NPY reduces [3H]NA release through affecting adenylate cyclase and the processes responsible for calcium mobilization.