Nitric oxide (NO) increases acetylcholine release from and inhibits smooth muscle contraction of guinea-pig gastric fundus.

Experiments were carried out to investigate the interaction between nitric oxide (NO) and cholinergic neurotransmission in smooth muscle strips of guinea-pig gastric fundus. Electrical field stimulation (2 Hz, 1 ms, 360 shocks) evoked atropine-sensitive contractions. Dimethylphenylpiperazinium (DMPP) (100 microM), a nicotinic receptor agonist, reversed the stimulation-evoked contraction and resulted in relaxation. Nomega-nitro-L-arginine (L-NNA) (100 microM), an NO synthase inhibitor, significantly increased the amplitude of stimulation-evoked contraction and abolished the effect of DMPP. Electrical stimulation increased the release of [3H]acetylcholine ([3H]ACh) from the tissue strips above the basal levels. Neither L-NNA (100 microM) nor DMPP (100 microM) alone influenced the basal release of [3H]ACh. Nomega-nitro-L-arginine (100 microM) decreased the electrical stimulation-evoked release of [3H]ACh. Dimethylphenylpiperazinium increased the stimulation-evoked release of [3H]ACh but had no effect in the presence of L-NNA. It is suggested that in guinea-pig gastric fundus, endogenous NO released in response to field stimulation has an opposite effect at the pre- and postsynaptic sites: it increases the release of ACh from cholinergic nerve terminals but reduces smooth muscle responses to ACh.