Neuropeptide Y in rat detrusor and its effect on nerve-mediated and acetylcholine-evoked contractions

1. Immunohistochemical and isolated organ bath techniques were used to detect the presence of neuropeptide Y (NPY) in the rat urinary bladder and to determine its effect on tone, spontaneous activity and contractile responses of the detrusor muscle to electrical field stimulation, acetylcholine and alpha,beta-methylene ATP (alpha,beta-MeATP). 2. A very rich presence of NPY-immunoreactive nerve fibres was found mainly within the bundles of detrusor muscle cells. Chronic treatment with 6-hydroxydopamine did not affect the density of NPY-positive nerve fibres. 3. NPY (> 1 nM) enhanced the force and frequency of spontaneous contractions and generated a rise in the resting tone of the detrusor. These effects of NPY on the tone and the spontaneous activity remained unaffected by atropine (3 microM), indomethacin (10 microM) and aspirin (100 microM) but were abolished by Ca(2+)-withdrawal from the bathing medium. 4. The enhancing effects of NPY on the spontaneous contractions and the resting tone were not prevented by the induction of purinoceptor desensitization. 5. NPY (1-250 nM) potentiated electrical field stimulation (EFS, 1-64 Hz, 0.1 ms pulses duration, 10s train duration)-evoked, tetrodotoxin (0.5 microM)-sensitive contractions. The atropine (3 microM)-resistant component of EFS-evoked contractions was also potentiated by NPY. By contrast, the nifedipine (1 microM)-resistant but atropine-sensitive component of EFS-evoked contraction was inhibited by NPY. 6. NPY (250 nM) did not affect acetylcholine-evoked contractions, but potentiated alpha,beta-MeATP-evoked contractions. 7. It is concluded that NPY-innervation of rat urinary bladder is largely confined to the detrusor muscle and is abundant and mainly non-adrenergic. It is further concluded that the enhancing effect of NPY on detrusor spontaneous activity and tone is caused by Ca2+ influx through nifedipine-sensitive Ca2+ channels and is not mediated through acetylcholine or cyclo-oxygenase-sensitive eicosanoids or ATP.8. The results are consistent with the hypothesis that intrinsic NPY in the rat detrusor innervation contributes to the motor transmission in two ways: by promoting non-cholinergic motor transmission and by inhibiting prejunctionally the cholinergic transmission.