Nitric oxide modulates cholinergic neurotransmission in cat duodenum.

1. Longitudinal muscle strips isolated from cat proximal duodenum were characterized by spontaneous phasic contractions. 2. Electrical field stimulation (EFS) (0.5 ms, 1-20 Hz, supramaximal voltage intensity for 40 sec) produced frequency-dependent contractions, and maximal amplitude was achieved at 10 Hz. The EFS-induced contractions were abolished either by atropine (10(-6) M) or by tetrodotoxin (3 x 10(-7) M). 3. The nitric oxide (NO) synthase blocker N infinity-nitro-L-arginine (L-NNA, 10(-4) M) or the inhibitor of the soluble guanylyl cyclase methylene blue (MB, 3 x 10(-5) M) increased the amplitude of the electrically evoked contractions. 4. L-Arginine (10(-3) M) or sodium nitroprusside (SNP, 10(-4) M) significantly decreased the amplitude of the EFS-induced, L-NNA- or MB-potentiated contractions as the effect of SNP was much more pronounced. 5. Neither L-NNA nor MB affected the contraction evoked by exogenous acetylcholine. 6. The L-NNA or MB-induced interruption of the L-arginine-NO pathway potentiated the electrically evoked cholinergic contractions, suggesting the inhibitory role of NO in the cholinergic neurotransmission realized probably at the pre-synaptic level in cat duodenum.