Nitric oxide modulates release of noradrenaline in guinea-pig gastric fundus.

The interaction between nitric oxide (NO) and the release of [(3)H]noradrenaline ([(3)H]NA) in conditions of non-activated and activated nicotinic receptors in guinea-pig gastric fundus preincubated with [(3)H]NA was studied. Nicotinic receptor agonist, 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) (100 microM) significantly increased the resting release of [(3)H]NA. NO-synthase inhibitor, N(omega)-nitro-L-arginine (L-NNA) (100 microM) significantly decreased DMPP-induced release of [(3)H]NA. Field electrical stimulation (FES) (2Hz; 1 ms; 360 st) significantly increased the release of [(3)H]NA above the basal levels. L-NNA significantly decreased the stimulation-evoked release of [(3)H]NA. DMPP increased the stimulation-evoked release of [(3)H]NA, effect which was significantly decreased by L-NNA. The data suggests that endogenous NO increases the release of [(3)H]NA, evoked either by activation of the nicotinic receptors or by electrical stimulation in guinea-pig gastric fundus.

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.

Modulation of electrically evoked responses in rat duodenum by activation of nicotinic cholinoceptors.

1. The effect of activation of nicotinic cholinoceptors in rat duodenal segments following electrical field stimulation (EFS) was investigated. 2. Electrical field stimulation elicited a two-component response: transient relaxation followed by contraction. The EFS-evoked response was tetrodotoxin (TTX; 1 mumol/L) sensitive. The relaxation component was NG-nitro-L-arginine (L-NNA; 100 mumol/L) sensitive, while the contractile response was atropine (1 mumol/L) sensitive. 3. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP; 20 mumol/L) induced relaxation of spontaneously active preparations that was L-NNA sensitive. L-Arginine (1 mmol/L) reversed the effects of L-NNA on DMPP-induced relaxation. 4. When EFS was applied, DMPP increased the amplitude of the relaxation component of the response and reduced the contractile component. 5. In the presence of L-NNA, the effect of DMPP on the relaxation component of the response to EFS was reduced, but the contractile response was not affected. L-Arginine partly reduced this effect of L-NNA. 6. Neither propranolol (1 mumol/L) nor yohimbine (1 mumol/L) had any effect on the actions of DMPP on EFS-evoked responses, but prazosin (1 mumol/L) strongly reduced the effect of DMPP on the contractile component of the response to EFS and slightly reduced the effect of DMPP on the relaxation response. 7. Histochemical studies demonstrated that, in the myenteric plexus of the rat duodenum, there are many reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons and that their number decreased after treatment with L-NNA. In the presence of L-arginine and L-NNA, the number of NADPH-d-positive neurons was similar to that found in control samples. 8. The data suggest that activation of nicotinic cholinoceptors modulates EFS-evoked responses in the rat duodenum as a result of the potentiation of nitrergic and adrenergic neurotransmission.

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.