Neuronal and endothelium‐derived mediators in the modulation of the gastric microcirculation: integrity in the balance

Whittle, Brendan J.R.

doi:10.1111/j.1476-5381.1993.tb13763.x

Cited by 136 publications

(75 citation statements)

References 220 publications

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“…Adventitial NANC nerves similarly relax pelvic, cerebral and mesenteric arteries by releasing NO, thereby mediating penile erection, in which neuronal synthesis of NO dominates over endothelial (Toda & Okamura, 1990;Ahlner, Ljusegren, Grundstrom & Axelsson, 1991;Burnett et al 1992). It is also possible that NANC-derived NO modulates gastric mucosal flow (Whittle, 1993). It is presently unknown whether mechanical forces acting on the vessel wall influence this neurogenic source of NO release.…”

Section: Flow-induced Release Of Endothelium-dependent Agonistsmentioning

confidence: 99%

“…There is nevertheless convincing evidence that the more biologically stable neurotransmitter peptides VIP and substance P can diffuse from adventitial nerves in salivary gland and skeletal muscle, respectively, and mediate vasodilatation by stimulating endothelial receptors (Persson, Hedqvist & Gustafsson, 1991;Edwards & Garrett, 1993). Neuropeptides such as calcitonin gene-related peptide may similarly contribute to mucosal blood flow in the gastrointestinal trace by stimulating EDRF synthesis (Whittle, 1993). Non-cholinergic, non-adrenergic (NANC) nerves themselves synthesize NO, thereby regulating smooth muscle tone and motility in the gastrointestinal and urinary tracts (Desai, Sessa & Vane, 1991;Burnett, Lowenstein, Bredt, Chang & Snyder, 1992).…”

Section: Flow-induced Release Of Endothelium-dependent Agonistsmentioning

confidence: 99%

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Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

Tm¹

1994

Experimental Physiology

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Section: Flow-induced Release Of Endothelium-dependent Agonistsmentioning

confidence: 99%

Section: Flow-induced Release Of Endothelium-dependent Agonistsmentioning

confidence: 99%

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

Tm¹

1994

Experimental Physiology

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“…1 The importance of these mediators is exempli®ed by the fact that suppression of mucosal prostaglandin or NO synthesis renders the gastrointestinal tract more susceptible to injury. 2,3 In recent years, it has been clearly demonstrated that enzymes responsible for the synthesis of prostaglandins and NO exist in multiple isoforms. Two forms of the cyclo-oxygenase (COX) enzyme have been characterized.…”

Section: Introductionmentioning

confidence: 99%

Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats

Davies

Sharkey

Asfaha

et al. 1997

Aliment Pharmacol Ther

125

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Background:Cyclo‐oxygenase‐1 (COX‐1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo‐oxygenase‐2 (COX‐2) is induced at sites of inflammation. Little is known about the regulation of COX‐2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX‐1 and COX‐2 expression shortly after administration of NSAIDs or ethanol.Methods:Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT‐PCR of COX‐1 and COX‐2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured.Results:Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX‐2 mRNA expression and a marked increase in COX‐2 immunoreactivity, particularly in the superficial mucosa. Expression of COX‐1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre‐treatment with prostaglandin E2 prevented the induction of COX‐2 by aspirin. Salicylate and indomethacin caused modest increases in COX‐2 immunoreactivity but no change in COX‐2 mRNA. Neither concentration of ethanol affected COX‐2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury.Conclusions:These results demonstrate a rapid up‐regulation of COX‐2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.

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“…In addition, since vagotomy affected basal fractional islet blood flow, the vagus nerve may regulate blood flow distribution within the pancreas (Iwase et al 2003). NO is a potent vasodilator and has also been shown to play an important role in regulating the gastric mucosal microcirculation (Whittle, 1993).…”

Section: Local Effects Of Cholecystokinin and Gastrin In The Gutmentioning

confidence: 99%

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

et al. 2006

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The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK 1 and CCK 2 receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.

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Neuronal and endothelium‐derived mediators in the modulation of the gastric microcirculation: integrity in the balance

Cited by 136 publications

References 220 publications

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

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