INHIBITORY EFFECT OF NEUROPEPTIDE-Y ON ADRENERGIC AND CHOLINERGIC TRANSMISSION IN RAT URINARY-BLADDER AND URETHRA

The effects of porcine neuropeptide Y (NPY) on electrically evoked release of [H-3]norepinephrine ([H-3]NE) and [H-3]acetylcholine ([H-3]ACh) were investigated in isolated preparations of the rat lower urinary tract. In the urethra, NPY (0.02-0.5 mu M) decreased the release of [H-3]NE in a dose-dependent manner (10-53%). In the bladder base the inhibitory effect of NPY on [H-3]NE release was not dose dependent. A low concentration (0.1 mu M) decreased the release (38%), whereas a high concentration (0.5 mu M) had no effect. However, in atropine-treated preparations, 0.5 mu M NPY elicited a significant inhibition (43%). These observations suggest that 0.5 mu M NPY elicits two opposing actions: a direct inhibitory action on adrenergic terminals and an indirect disinhibitory action to eliminate heterosynaptic cholinergic inhibition of [H-3]NE release. In both tissues the action of NPY on [H-3]NE release was not significantly modified by the alpha-adrenergic blocking agent yohimbine (1 mu M). [H-3]ACh release in the bladder body was not altered by 0.1 mu M: NPY but was suppressed (39%) by 1 mu M NPY. The effect of NPY (1 mu M) on [H-3]ACh release was dependent on the frequency of stimulation. NPY suppressed the release at 2-Hz stimulation but had no significant effect at 20 Hz. These results suggest that NPY may have an important role in the neural regulation of the lower urinary tract by exerting differential effects on the release of cholinergic and adrenergic transmitters via autoinhibition and heterosynaptic interactions.