Functional evidence for the presence of nitric oxide synthase in the dorsal motor nucleus of the vagus

doi:10.1016/0016-5085(95)90634-7

Gastroenterology

Volume 109, Issue 5, November 1995, Pages 1484-1491

https://doi.org/10.1016/0016-5085(95)90634-7 Get rights and content

Abstract

$Background & Aims$ Histochemical studies indicate that reduced nicotinamide adenine dinucleotide phosphate diaphorase, the nitric oxide synthase-related enzyme, is present in the dorsal motor nucleus of the vagus of the cat. We have previously shown in vitro that NO synthase is present in this nucleus in the rat and that the excitatory effect of N-methyl-d-aspartate on these neurons is in part caused by NO formation. The aim of this study was to obtain functional evidence for the presence of NO synthase in the cat dorsal motor nucleus of the vagus. $Methods$ l-Glutamate, l-arginine, d-arginine, the NO donor S-nitroso-N-acetyl-penicillamine, and the NO synthase inhibitor N^G-nitro-l-arginine-methyl ester were unilaterally microinjected into the rostral dorsal motor nucleus of anesthetized cats, and antral and pyloric motility were monitored using extraluminal force transducers. $Results$ Microinjection of l-arginine increased gastric motility, whereas d-arginine had no effect. Vagotomy eliminated the l-arginine-induced increases. Microinjection of S-nitroso-N-acetylpenicillamine increased antral motility. N^G-Nitro-l-arginine-methyl ester prevented l-arginine from exerting an effect on gastric motility. $Conclusions$ Motility increases obtained after microinjection of l-arginine into the dorsal motor nucleus and prevention of these motility increases with microinjection of a NO synthase inhibitor provide functional evidence for the presence of NO synthase in the dorsal motor nucleus of the vagus in the cat.

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Acupuncture has been used for treating functional gastrointestinal (GI) disorders. Animal studies demonstrated that acupuncture improves various stress-induced physiological responses. We investigated the effects of electroacupuncture (EA) at ST-36 (Zusanli; lower limb) on stress-induced delay of gastric emptying. Solid food gastric emptying in 90 min was significantly delayed by restraint stress (27.3 ± 2.1%, n = 8), compared to that of controls (64 ± 2.1%, n = 8). Restraint stress-induced delay of gastric emptying was significantly restored by the intracisternal (IC)-injection of GABA_A receptor antagonist, bicuculline methiodide (46.5 ± 3.1%; n = 6) and GABA_B receptor antagonist, phaclofen (48 ± 3.3%; n = 6). Delayed gastric emptying induced by restraint stress was significantly improved by EA at ST-36 (49.7 ± 1.4%). The stimulatory effect of EA on stress-induced delay of gastric emptying was prevented by pretreatment with IC-injection of glutamate receptor antagonist, kynurenic acid (30.1 ± 2.1%). In conclusion, restraint stress-induced delay of gastric emptying is mediated via central GABA_A and GABA_B receptors. EA at ST-36 stimulates glutaminergic neurons in the brainstem resulting in improvement of stress-induced delay of gastric emptying.
Stimulatory effects of centrally injected nitric oxide donors on gastric acid secretion in anesthetized rats
2002, Japanese Journal of Pharmacology
The effects of centrally injected nitric oxide (NO) donors on gastric acid secretion were investigated in continuously perfused stomach of anesthetized rats. The lateral cerebroventricular (LV) injection of NOC5 (30- 100 μ g) and NOC12 (10- 100 μ g) dose-dependently stimulated gastric acid secretion. The LV injection of NOC18 (30 μ g) also stimulated gastric acid secretion. The other type of NO donor, sodium nitroprusside (3-30 μ g, LV), also dose-dependently stimulated gastric acid secretion. The effect of NOC5 at 100 μ g was blocked by carboxy-PTIO, an NO scavenger, and by cervical vagotomy. Furthermore, NOC12 (30, 100 μ g) dose-dependently stimulated gastric acid secretion in pylorus-ligated conscious rats. These results suggest that centrally injected NO donors stimulate gastric acid secretion in both conscious and anesthetized rats through vagus activation.
Effects of nitric oxide in the dorsal motor nucleus of the vagus on the extrahepatic biliary system in rabbits
2001, Autonomic Neuroscience: Basic and Clinical
To investigate whether nitric oxide (NO) in the dorsal motor nucleus of the vagus (DMV) mediated an influence on the extrahepatic biliary system, we studied the effects of microinjection of NO-producing drugs into DMV on the motilities of the gallbladder (GB) and the sphincter of Oddi (SO) in anesthetized rabbits. Microinjection of the NO precursor l-arginine into the rostral DMV produced an increase in the GB and SO motilities, which can be counteracted by both N^G-nitro-l-arginine-methyl (l-NAME), an inhibitor of NOS, and reduced hemoglobin (rHb), a scavenger of NO, and were eliminated by bilateral cervical vagotomy. On the other hand, the NO donor sodium nitroprusside (SNP) was able to mimic the excitatory effect of l-arginine. This effect can be antagonized by rHb, but not by l-NAME, for SNP supplied exogenous NO without activating NOS. These results indicate that NO in the DMV mediates an excitatory effect on the extrahepatic biliary system.
Chapter VI Nitric oxide systems in the medulla oblongata and their involvement in autonomic control
2000, Handbook of Chemical Neuroanatomy
This chapter describes the location of nitric oxide synthase (NOS)-immunoreactive (NOS-IR) neurones and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurones in the medulla of the rat and presents an anatomical evidence for the functional role of nitrergic neurones in the medulla by (1) examining the extent of the co-localization of NOS-IR with immunoreactivities for other neuronal markers, (2) presenting data concerning the presence of NOS in vagal afferent and efferent neurones, and (3) analyzing the synaptic relationships between vagal afferents and NOS-IR neurones in the dorsal vagal complex. The chapter discusses results in relation to those from other anatomical, pharmacological, and physiological studies that have strongly implicated the involvement of neuronal NO as a potential transmitter in autonomic, somatosensory, and viscerosensory pathways at the level of the medulla oblongata, in addition to its well-established functions in neuronal development and neurodegeneration. Two different methods have been used to map the distribution of nitric oxide-producing neurones in the central nervous system: the NADPH-diaphorase histochemical method and the later immunohistochemical method using antisera raised against NOS.
Gastric stasis in neuronal nitric oxide synthase-deficient knockout mice
2000, Gastroenterology
Citation Excerpt :
Such marked hypertrophy is not observed in these mutant mice. nNOS has been shown to localize to the intrinsic gastric inhibitory motor nerve endings, intrinsic interneurons, preganglionic motor neurons in the caudal dorsal motor nucleus of the vagus that project to the stomach, and the nucleus tractus solitarius neurons that are premotor to dorsal motor nucleus of the vagus neurons.26,27 nNOS deficiency would disrupt NO neurotransmission at all these sites and result in selective but total loss of nitrergic inhibitory neurotransmission throughout the body, including the stomach.
Background & Aims: Nitric oxide (NO) is a major inhibitory neurotransmitter in the gut. This study aimed to identify the effect of chronic deprivation of NO derived from neuronal (nNOS) or endothelial (eNOS) nitric oxide synthase on gastric emptying. Methods: nNOS-deficient (knockout) mice were compared with wild-type mice for gastric size, fluoroscopic appearance after gavage of contrast, and histology of the pyloric sphincter. Wild-type mice treated with the NOS inhibitor N^ω-nitro L-arginine (L-NA) and eNOS-deficient mice were also compared with wild-type and nNOS-deficient mice for liquid and solid gastric emptying. Results: nNOS-deficient mice showed gastric dilation. Fluoroscopy showed delayed gastric emptying of radiologic contrast. There was no marked localized hypertrophy or luminal narrowing at the pyloric sphincter by histology of relaxed wild-type, nNOS-deficient, and eNOS-deficient tissues. Gastric emptying of both solids (28% ± 27%) and liquids (22% ± 18%) was significantly delayed in nNOS-deficient mice compared with control wild-type mice (82% ± 22% for solids; 48% ± 17% for liquids). eNOS-deficient mice showed no significant difference from wild-type mice (74% ± 28% for solids; 47% ± 23% for liquids). Wild-type mice treated acutely with L-NA showed delay in emptying of solids (43% ± 31%) but not liquids (39% ± 15%). Conclusions: Chronic depletion of NO from nNOS, but not eNOS, results in delayed gastric emptying of solids and liquids.
GASTROENTEROLOGY 2000;119:766-773
Effect of nitric oxide synthase inhibition on plasma motilin release in fasted dogs
1997, Regulatory Peptides
Inhibition of nitric oxide (NO) synthase on plasma motilin concentrations is not known. The aim of this study was to examine the effect of NO synthesis inhibitor on gastrointestinal motility and motilin release in conscious dogs. Dogs fitted with force transducers were given N^ω-nitro-L-arginine (L-NNA) after the termination of phase III contractions. Blood samples were taken for measurement of motilin concentrations. L-NNA induced phase III-like contractions in the stomach and duodenum in association with a significant increase in motilin level. Atropine or hexamethonium significantly inhibited L-NNA-induced phase III-like contractions and the increase in motilin level. Ondansetron markedly inhibited gastric, but not duodenal, phase III-like contractions without affecting the increase in motilin level caused by L-NNA. Vagotomy affected neither the occurrence of phase III-like contractions nor the increase in motilin level produced by L-NNA. We conclude that inhibition of NO synthesis stimulates motilin release via cholinergic pathways independent of the vagus, and induces phase III-like contractions in the stomach and duodenum. Phase III-like contractions induced by L-NNA are mediated through the activation of 5-HT₃ receptors.

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^☆

Supported by National Institutes of Health grants 2 ROI DK 2 997509A1 and 5 T32 GM 08386.

The authors thank Christa Highley for excellent typing of the manuscript.

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Functional evidence for the presence of nitric oxide synthase in the dorsal motor nucleus of the vagus☆

Abstract

Life Sci

Eur J Pharmacol

Gastroenterology

Neuron

Brain Res

Eur J Pharmacol

Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle

Clin Exp Pharmacol Physiol

The effects of l-arginine and NGmonomethyl-l-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation

Br J Pharmacol

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

Nature

Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission

Am J Physiol

Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter

Am J Physiol

Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo

Am J Physiol

Involvement of CCK and nitric oxide in transient lower esophageal sphincter relaxation to gastric distension in dogs

Gastroenterology

CNS inhibition of gastric motor function via nitric oxide pathways in the hindbrain

Gastroenterology

NO in the brain regulates colonic motor activity

Gastroenterology

Brain NO synthase regulates upper gastrointestinal fasting motor activity

Gastroenterology

Localization of sites within dorsal motor nucleus of vagus that affects gastric motility

Am J Physiol

Control centers in the central nervous system for regulating gastrointestinal motility

Neurology of the Gut

The effects of l-arginine and N^Gmonomethyl-l-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation