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 rel ease 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 inh ibitory 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 p reparations, 0.5 mu M NPY elicited a significant inhibition (43%). The se observations suggest that 0.5 mu M NPY elicits two opposing actions : a direct inhibitory action on adrenergic terminals and an indirect d isinhibitory action to eliminate heterosynaptic cholinergic inhibition of [H-3]NE release. In both tissues the action of NPY on [H-3]NE rele ase was not significantly modified by the alpha-adrenergic blocking ag ent yohimbine (1 mu M). [H-3]ACh release in the bladder body was not a ltered by 0.1 mu M: NPY but was suppressed (39%) by 1 mu M NPY. The ef fect of NPY (1 mu M) on [H-3]ACh release was dependent on the frequenc y of stimulation. NPY suppressed the release at 2-Hz stimulation but h ad no significant effect at 20 Hz. These results suggest that NPY may have an important role in the neural regulation of the lower urinary t ract by exerting differential effects on the release of cholinergic an d adrenergic transmitters via autoinhibition and heterosynaptic intera ctions.