The role of nitric oxide in inhibitory non‐adrenergic non‐cholinergic neurotransmission in the canine lower oesophageal sphincter

Man, Joris G. De; Pelckmans, Paul; Boeckxstaens, Guy E.; Bult, Hidde; Oosterbosch, L; Herman, Arnold G.; Maercke, Y. M. Van

doi:10.1111/j.1476-5381.1991.tb12305.x

Cited by 97 publications

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References 31 publications

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“…The important role of NO in LOS relaxation was suggested for the first time in 1991 from experiments studying the effect of NOS inhibitors on opossum LOS muscle strips ( Murray et al , 1991 ; Tottrup et al , 1991 ) and later confirmed on human tissue ( Oliveira et al , 1992 ; Tottrup et al , 1993 ). Further experiments showed that NO is the main neurotransmitter that mediates smooth muscle LOS relaxation in different species such as dogs, guinea‐pigs, rats, cats and pigs ( de Man et al , 1991 ; Murray et al , 1991 ; Kortezova et al , 1996 ; Yuan et al , 1998 ; Farre et al , 2006 , 2007b ).…”

Section: Nitric Oxidementioning

confidence: 99%

Regulation of basal tone, relaxation and contraction of the lower oesophageal sphincter. Relevance to drug discovery for oesophageal disorders

Farré¹,

Sifrim²

2008

British J Pharmacology

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The lower oesophageal sphincter (LOS) is a specialized region of the oesophageal circular smooth muscle that allows the passage of a swallowed bolus to the stomach and prevents the reflux of gastric contents into the oesophagus. The anatomical arrangement of the LOS includes semicircular clasp fibres adjacent to the lesser gastric curvature and sling fibres following the greater gastric curvature. Such anatomical arrangement together with an asymmetric intrinsic innervation and distinct proportion of neurotransmitters in both regions produces an asymmetric pressure profile. The LOS tone is myogenic in origin and depends on smooth muscle properties that lead to opening of L-type Ca 2 þ channels; however it can be modulated by enteric motor neurons, the parasympathetic and sympathetic extrinsic nervous system and several neurohumoral substances. Nitric oxide synthesized by neuronal NOS is the main inhibitory neurotransmitter involved in LOS relaxation. Different putative neurotransmitters have been proposed to play a role together with NO. So far, only ATP or related purines have shown to be co-transmitters with NO. Acetylcholine and tachykinins are involved in the LOS contraction acting through acetylcholine M 3 and tachykinin NK 2 receptors. Nitric oxide can also be involved in the regulation of LOS contraction. The understanding of the mechanisms that originate and modulate LOS tone, relaxation and contraction and the characterization of neurotransmitters and receptors involved in LOS function are important to develop new pharmacological tools to treat primary oesophageal motor disorders and gastro-oesophageal reflux disease.

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Section: Nitric Oxidementioning

confidence: 99%

Regulation of basal tone, relaxation and contraction of the lower oesophageal sphincter. Relevance to drug discovery for oesophageal disorders

Farré¹,

Sifrim²

2008

British J Pharmacology

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Nitric oxide producing neurons in the monkey and human digestive system

Giorgio

Parodi

Brecha

et al. 1994

J of Comparative Neurology

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Nitric oxide has been proposed as an inhibitory transmitter molecule that plays a role in muscle relaxation and vasodilation in the gastrointestinal tract. The present study analyzes the distribution of nitric-oxide-producing neurons in the monkey and human digestive system by means of nicotinamide-adenine-dinucleotide-phosphate-diaphorase histochemistry. This histochemical method is reliable and convenient for the visualization of neuronal nitric-oxide synthase, the enzyme responsible for nitric-oxide generation. In the gastrointestinal tract, nitric-oxide-synthase-related diaphorase activity was present in nerve fibers running throughout the muscular layer (circular > longitudinal) and in numerous ganglion cells and processes in the myenteric plexus of monkeys and humans. Labelled ganglion cells and fibers also were observed in the submucous plexus, although they were much less numerous than those seen in the myenteric plexus. In the submucosa, a few positive fibers were seen around blood vessels. In the mucosa, stained fibers were sparse at the base of the villi and crypts, whereas they were quite abundant in the muscularis mucosae, especially in the small intestine and colon. In the gallbladder (human), labelling was found in ganglion cells and processes of the innermost and outermost ganglionated plexuses. Stained fibers also were distributed to the muscular layer and, less abundantly, to the mucosa and vasculature. Labelled fibers were more abundant in the sphincter of Oddi (human) than in the gallbladder. In the monkey and human pancreas, nicotinamide-adenine-dinucleotide-diaphorase staining was seen mainly in ganglion cells and fibers of intrapancreatic ganglia, and in processes running among acini, around ducts and in the stroma. A moderate density of stained fibers also was distributed to the vasculature, whereas the islets showed few positive processes. Finally, double label experiments performed in the pancreas showed that the vast majority of neurons producing nitric oxide are immunoreactive for vasoactive intestinal peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

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