Effects of NG-nitro-L-arginine on electrical and mechanical responses to stimulation of non-adrenergic, non-cholinergic inhibitory nerves in circular muscle of the rat gastric fundus

doi:10.1016/0014-2999(93)90690-J

European Journal of Pharmacology

Volume 231, Issue 1, 26 January 1993, Pages 103-109

https://doi.org/10.1016/0014-2999(93)90690-J Get rights and content

Abstract

The effects of L-nitroarginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, on non-adrenergic, non-cholinergic inhibitory transmission in the circular smooth muscle of the rat gastric fundus were studied. The relaxation in response to nerve stimulation in the presence of guanethidine and atropine was depressed by the application of L-NNA (10⁻⁴ M), and the depression was reversed by the addition of L-arginine (10⁻⁴ M). The time course of the relaxation was altered from a monophasic to biphasic one, both of which were depressed. Stimulation of non-adrenergic, non-cholinergic nerves initiated inhibitory junctional potentials (i.j.p.). In addition, slow after-hyperpolarization was observed when stimuli were applied repeatedly at frequencies higher than 0.5 Hz. L-NNA reduced the i.j.p. partially and abolished the after-hyperpolarization, indicating the partial involvement of NO in non-adrenergic, non-cholinergic inhibitory transmission. The effects of L-NNA on the nerve-mediated relaxation are thought to be due to changes in the i.j.p. and slow after-hyperpolarization.

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We investigated the effect of the ascorbic acid on the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-stained and myosin-V myenteric neurons in the ileum of chronically diabetic rats. The study was performed 4 months after inducing experimental diabetes with streptozotocin. Diabetic rats showed increased (p<0.05) glycaemia and glycated haemoglobin. Three groups were compared, i.e., nondiabetic rats, diabetic rats and diabetic rats treated with ascorbic acid. Myosin-V immunohistochemistry and NADPH-d histochemistry were employed. We investigated the areas of 500 cell bodies of myosin-V neurons and of 500 NADPH-d-stained neurons from all groups. The quantitative analysis was performed by using an area of 8.96 mm² from each ileum. The two groups of diabetic rats and diabetic rats treated with ascorbic acid showed reduction in the number and an increased area of the myosin-V-immunostained myenteric neurons. In addition, we observed increased relative proportion of NADPH-d-stained neurons in diabetic rats and diabetic rats treated with ascorbic acid. However, the area of these neurons in the diabetic rats group was larger than those evidenced in the nondiabetic rats and diabetic rats treated with ascorbic acid.
Non-adrenergic non-cholinergic relaxation of the rat stomach
1998, General Pharmacology
- 1.
  Receptive and adaptive relaxations of the proximal third of the stomach are reflex responses that enable the stomach to accommodate large volumes with minimal increases in intraluminal pressure. The smooth muscle relaxations are termed non-adrenergic non-cholinergic (NANC).
- 2.
  Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are considered to be the principal neurotransmitters of NANC relaxation of the rat stomach. NO appears to be mainly responsible for the speed of the relaxation and VIP appears to be responsible for the duration.
- 3.
  Studies indicate that inhibitory neurons may also release other neurotransmitters, such as adenosine triphosphate (ATP) and peptide histidine isoleucine (PHI).
- 4.
  NANC relaxation of the rat stomach is a complex phenomenon that appears to involve many neurotransmitters, each with a specific role.
Regional differences in the nitrergic innervation between the proximal and the distal colon in rats
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Background & Aims: Functional differences in the inhibitory neural pathway between the proximal and the distal colon are unknown. Methods: We investigated the nonadrenergic, noncholinergic (NANC) relaxation, nitric oxide synthase (NOS) synthesis, and NOS messenger RNA (mRNA) expression of the myenteric plexus in the proximal and the distal colon in rats. Results: Transmural nerve stimulation of the neuromuscular preparations from the proximal colon showed greater NANC relaxations than those from the distal colon. NANC relaxations were abolished by the NO biosynthesis inhibitor (N^G-nitro-L-arginine methyl ester) in the proximal and the distal colon, suggesting mediation by NO released from the myenteric plexus. The average number of NOS-immunoreactive cells was significantly higher in the tissue from the proximal colon than in the tissue from the distal colon. Western and Northern blot analyses showed a higher density of the immunoreactive NOS band and the NOS mRNA band in the tissue from the proximal colon than in that from the distal colon. Conclusions: These observations indicate that the number of NOS-containing neurons and the NOS activity are increased in the myenteric plexus of the proximal colon compared with the distal colon, resulting in greater NANC relaxation in the proximal colon. These findings may explain the physiological role of the proximal colon as an organ for fecal storage and absorption of excess fluid.
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Evaluation of an electrochemical microprobe for direct NO measurement in the rat gastric fundus
1997, Journal of Pharmacological and Toxicological Methods
Nitric oxide (NO) is an inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter in the rat gastric fundus and is released upon electrical or pharmacological stimulation of the inhibitory NANC neurons. In this study, it was attempted to measure the release of NO from the rat gastric fundus upon electrical stimulation or administration of nicotine directly via an electrochemical probe (ISO-NO). The system was evaluated by adding exogenous NO. Addition of exogenous NO induced concentration-dependent relaxations of the rat gastric fundus and an increase in the ISO-NO probe baseline current. The concentration of NO detected by the ISO-NO probe was lower than the concentration of NO administered. When no tissue was present, higher concentrations of NO were detected than in the presence of a tissue. In the absence of $95% O_{2} 5% CO_{2}$ the concentration of NO detected was highest. Electrical stimulation induced relaxations of the rat gastric fundus which were reduced by N^G-nitro-l-arginine methylester (l-NAME). An increase in the ISO-NO probe baseline current was also observed, but this was due to nonspecific effects as the response also occurred without a tissue present and was not sensitive to l-NAME. Nicotine induced relaxations, which were reduced by l-NAME, but the ISO-NO probe baseline current remained unaltered, even in the presence of l-arginine plus superoxide dismutase. It can be concluded that it is not possible to detect directly the NO release from the rat gastric fundus upon electrical or pharmacological stimulation of the NANC neurons with the ISO-NO probe.
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1997, European Journal of Pharmacology
The effects of amiloride on contraction evoked by perivascular nerve stimulation were studied in a ring preparation of rat mesenteric artery. The contraction evoked by nerve stimulation was abolished by tetrodotoxin or prazosin. Amiloride depressed the nerve-induced contraction concentration dependently. Noradrenaline induced a tonic contraction in the artery. Amiloride inhibited the noradrenaline-induced contraction concentration dependently. The excitatory junctional potential (e.j.p.) recorded intracellularly was abolished by tetrodotoxin. The amplitude of the e.j.p. was not altered by prazosin or amiloride. These results indicate that amiloride inhibits the perivascular nerve-mediated contraction of mesenteric artery mainly through postsynaptic adrenoceptor inhibition and not through mechanisms related to e.j.p.
Distension-evoked ascending and descending reflexes in the isolated guinea-pig stomach
1997, Journal of the Autonomic Nervous System
Distension-evoked gastric reflexes were studied by intracellular recording from circular muscle cells in the gastric fundus, corpus and antrum in the isolated guinea-pig stomach. Localised electrical stimulation, 2 mm circumferential to the recording electrode, evoked inhibitory junctions potentials in all three gastric regions, sometimes followed by depolarisations in the antrum. In the mid corpus, the inhibitory responses were substantially reduced by N^w-nitro-l-arginine (100 μM), unmasking excitatory junction potentials. Residual hyperpolarisations were blocked by apamin (0.5 μM) which also enhanced the amplitude of excitatory junction potentials. These excitatory junction potentials were abolished by hyoscine (1 μM). Thus transmission from inhibitory motor neurons is mediated by both nitric oxide and an apamin-sensitive mechanism. Transmission from excitatory motor neurons to the circular muscle is mediated by acetylcholine via muscarinic receptors. Balloon distension of 10 s duration of the fundus or antrum elicited inhibitory junction potentials in circular muscle cells of the mid corpus. These inhibitory junction potentials were blocked by tetrodotoxin (0.6 μM) and were greatly reduced by N^w-nitro-l-arginine (100 μM). The residual hyperpolarisations were blocked by apamin (0.5 μM). This indicates the presence of ascending and descending inhibitory reflex pathways in the stomach. In 3 out of 7 experiments, following blockade of inhibitory transmission, small nerve-mediated excitatory junction potentials were evoked by antral distension indicating the presence of an additional ascending excitatory reflex pathway. Distension of the corpus elicited prominent inhibitory junction potentials, sometimes followed by large depolarisations, in circular muscle cells in the fundus, but not in the antrum. This suggests that there is also an ascending inhibitory reflex pathway from the corpus to the fundus but no distension-sensitive descending reflex pathway from the corpus to the antrum. These results demonstrate that within the stomach there are reflex pathways which can be activated by localised distension and project at some distance orally and aborally within the gastric wall. It is likely that the inhibitory reflex pathways are involved in gastric adaptive relaxation which occurs when the intact, isolated stomach is distended. The excitatory reflex pathways from the antrum to the corpus are likely to be involved in the intrinsic excitatory reflex responses observed in the isolated intact stomach to distension and thus be involved in the mixing and emptying of gastric contents.

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Effects of NG-nitro-L-arginine on electrical and mechanical responses to stimulation of non-adrenergic, non-cholinergic inhibitory nerves in circular muscle of the rat gastric fundus

Abstract

Biochem. Biophys. Res. Commun.

Jap. J. Pharmacol.

Evidence for non-cholinergic, non-adrenergic transmission in the guinea-pig ileum

J. Physiol.

Release of nitric oxide upon stimulation of non-adrenergic non-cholinergic nerves in the rat gastric fundus

J. Pharmacol. Exp. Ther.

Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter

Nature

The non-adrenergic non-cholinergic nervous system

Arch. Int. Pharmacodyn.

Inhibition of the smooth muscle of the taenia coli

Nature

The inhibitory innervation of the taenia of the guinea-pig caecum

J. Physiol.

Non-cholinergic fast and slow post-stimulus depolarization in the guinea-pig ileum

J. Physiol.

Nitric oxide may be the final mediator of non-adrenergic, non-cholinergic inhibitory junction in the gut

Can. J. Physiol. Pharmacol.

Noncholinergic membrane potential responses to transmural nerve stimulation in the guinea pig ileum

Am. J. Physiol.

Involvement of nitric oxide synthetic pathway in inhibitory junctional potential in canine proximal colon

Am. J. Physiol.

Evidence for dual components in the non-adrenergic non-cholinergic relaxation in rat gastric fundus, role of endogenous nitric oxide and vasoactive intestinal polypeptide

J. Auton. Nerv. Syst.

Effects of N^G-nitro-L-arginine on electrical and mechanical responses to stimulation of non-adrenergic, non-cholinergic inhibitory nerves in circular muscle of the rat gastric fundus