Neuropeptide Y depresses reflex urinary bladder contractions in rats and modifies central activity of opioid agonists

The 36 amino acid peptide neuropeptide Y (NPY) has been found distributed in central structures associated with nociception and the actions of opioid analgesics. We therefore studied its central actions on reflex bladder contractions which we have shown to be inhibited by supraspinal and spinal opioid administrations in urethane anesthetized rats. Neuropeptide Y produced a dose related (0.5-2 micrograms per rat) inhibition of bladder contractions following intracerebroventricular (ICV) and spinal intrathecal (IT) administrations. These effects could not be antagonized by naloxone (2 micrograms, ICV or IT) or by ICI 174,864 [N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid] (3 micrograms, ICV or IT). NPY (0.5-1 micrograms) reduced the ICV and IT effects of morphine but potentiated the action of the selective delta-receptor ligand [2-D-penicillamine, 5-L-penicillamine] enkephalin (DPLPE). The effect of the mu-selective opioid ligand [D-Ala2, Me-Phe4, Gly(ol)5] enkephalin (DAGO) were unaffected as were the submaximal ICV and IT actions of noradrenaline. It was concluded that NPY-induced inhibition of bladder activity was not due to a direct opioid receptor interaction. However since NPY consistently changed the activity of opioids (morphine and DPLPE), this suggested a possible physiological role in the regulation of opioid receptors, central neural excitability and thereby visceral activity.