Neuropeptide Y neuromodulation of sympathetic co-transmission in the guinea-pig vas deferens.

1. We examined the neuromodulatory effects of neuropeptide Y (NPY) on purinergic and adrenergic co-transmission in the guinea-pig vas deferens. 2. In superfused vas deferens preparations, NPY (0.3 microM) inhibited the stimulus-evoked overflow of both ATP and [3H]-noradrenaline ([3H]-NA) at 2 Hz, but only the stimulus-evoked release of [3H]-NA at 20 Hz. 3. Postjunctionally, NPY greatly enhanced responses to alpha,beta-methylene ATP and to a lesser extent to exogenous NA. 4. Preparations stimulated in organ baths showed frequency-dependent contractions to field stimulation. NPY abolished responses to field stimulation at low frequency and a small number of pulses. At high frequency (20 Hz), NPY abolished responses elicited by 10 pulses, inhibited responses by 50% at 20 pulses and had little effect on preparations stimulated for 240 pulses. 5. Our study suggests that NPY neuromodulates co-transmission in the vas deferens by inhibiting the release of ATP and NA and that these effects predominate over the postjunctional enhancement by NPY. These results also show that the physiological effect of NPY will be determined both by the frequency at which the nerves are discharging and the duration of their firing.