Inhibition of gastric acid secretion by stress: A protective reflex mediated by cerebral nitric oxide

Esplugues, Juan V.; Barrachina, Dolores; Beltrán, Belén; Calatayud, Sara; Whittle, Brendan J.R.; Moncada, Salvador

doi:10.1073/pnas.93.25.14839

Cited by 47 publications

(50 citation statements)

References 29 publications

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“…More in detail, NO is implicated in neural signaling, neurotoxicity, synaptic plasticity, modulation or expression of pain, and in regulation of visceral secretion and/or visceral motility (Esplugues et al, 1996;Garcia-Zaragoza et al, 2000;Quintana et al, 2001).…”

Section: Discussion Of Resultsmentioning

confidence: 99%

Immunohistochemical characterization of TH13‐L2 spinal ganglia neurons in sheep (Ovis aries)

Russo

Clavenzani

Mazzoni

et al. 2009

Microscopy Res & Technique

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Spinal ganglia (SG) neurons are commonly classified according to various specific features. The most widespread classification based on morphological and ultrastructural features subdivides SG neurons into light and small dark neurons. Using immunohistochemical, histochemical and lectin methods, it is possible to further subdivide the small dark neurons into two subpopulations: peptidergic and nonpeptidergic neurons. The majority of studies on SG neurons were carried out on mice and rats; there are few or no studies on large mammals. In this study, some of the widely used neuronal markers, neurofilament 200 kDa (NF200), substance P (SP), calcitonin gene-related peptide (CGRP) and isolectin B4 (IB4), were employed to characterize neuronal nitric oxide synthase (nNOS)-immunoreactivity (-IR) in sheep (Ovis aries) SG (Th13-L2) neurons. The majority of the SG neurons were IB4-labeled (79 +/- 10%), followed by NF200- (45 +/- 4%), NOS- (44 +/- 10%), SP- (42 +/- 5%) and CGRP-IR (35 +/- 7%) neurons. The triple staining experiments showed that a higher percentage (75 +/- 16%) of NOS-IR neurons bound both IB4 and CGRP, or both IB4 and SP (49 +/- 6%). The IB4 marker showed an unexpected staining pattern; in fact, IB4-labeled neurons largely colocalized with NF200, usually considered a marker of light SG neurons, and with CGRP and SP. For this reason, IB4 cannot be employed in sheep to differentiate between light and dark neurons, or between peptidergic and nonpeptidergic neurons. These results suggest the importance of being cautious when comparing data among different species.

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Section: Discussion Of Resultsmentioning

confidence: 99%

Immunohistochemical characterization of TH13‐L2 spinal ganglia neurons in sheep (Ovis aries)

Russo

Clavenzani

Mazzoni

et al. 2009

Microscopy Res & Technique

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“…Nitric oxide donors, for example, have been observed to inhibit vagally stimulated gastric acid secretion without affecting basal or pentagastrinor histamine-stimulated acid production (4). Nitric oxide is hypothesized to serve as an intermediary in the gastric acid suppression induced by endotoxin, cytokines, or stress (13,14,27). Interestingly, while several orexigenic hormones have been implicated in vagal stimulation of gastric acid production, nesfatin is the only anorexigenic hormone confirmed to inhibit vagally mediated gastric acid production (11,28,46).…”

Section: Discussionmentioning

confidence: 99%

Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats

Xia

Fritze

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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MW. Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats. Am J Physiol Gastrointest Liver Physiol 303: G570 -G577, 2012. First published June 21, 2012; doi:10.1152/ajpgi.00178.2012.-Nesfatin-1, a novel hypothalamic peptide, inhibits nocturnal feeding behavior and gastrointestinal motility in rodents. The effects of nesfatin-1 on gastrointestinal secretory function, including gastric acid production, have not been evaluated. Nesfatin-1 was injected into the fourth intracerebral ventricle (4V) of chronically cannulated rats to identify a nesfatin dose sufficient to inhibit food intake. Nesfatin-1 (2 g) inhibited dark-phase food intake, in a dose-dependent fashion, for Ͼ3 h. Gastric acid production was evaluated in urethane-anesthetized rats. Nesfatin-1 (2 g) was introduced via the 4V following endocrine stimulation of gastric acid secretion by pentagastrin (2 g·kg Ϫ1 ·h Ϫ1 iv), vagal stimulation with 2-deoxy-D-glucose (200 mg/kg sc), or no stimulus. Gastric secretions were collected via gastric cannula and neutralized by titration to determine acid content. Nesfatin-1 did not affect basal and pentagastrin-stimulated gastric acid secretion, whereas 2-deoxy-D-glucosestimulated gastric acid production was inhibited by nesfatin-1 in a dose-dependent manner. c-Fos immunofluorescence in brain sections was used to evaluate in vivo neuronal activation by nesfatin-1 administered via the 4V. Nesfatin-1 caused activation of efferent vagal neurons, as evidenced by a 16-fold increase in the mean number of c-Fos-positive neurons in the dorsal motor nucleus of the vagus (DMNV) in nesfatin-1-treated animals vs. controls (P Ͻ 0.01). Finally, nesfatin-induced Ca 2ϩ signaling was evaluated in primary cultured DMNV neurons from neonatal rats. Nesfatin-1 caused dosedependent Ca 2ϩ increments in 95% of cultured DMNV neurons. These studies demonstrate that central administration of nesfatin-1, at doses sufficient to inhibit food intake, results in inhibition of vagally stimulated secretion of gastric acid. Nesfatin-1 activates DMNV efferent vagal neurons in vivo and triggers Ca 2ϩ signaling in cultured DMNV neurons. gastric hormones; intracellular calcium; dorsal motor nucleus of the vagus NESFATIN-1, an 82-amino acid peptide derived from the parent peptide nucleobindin-2, was first identified as a satiety molecule in the hypothalamus by Oh et al. (33). Inhibition of rodent nocturnal feeding behavior by nesfatin-1 administered into the intracranial ventricles has been consistently observed (18,25,34,40,42). Most centrally acting peptides that influence food intake also regulate the processes of digestion, including gastrointestinal motility and secretory function (45). In rodents, nesfatin-1 inhibits gastroduodenal motility and gastric empty-

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“…In animals, the role of acid in gastric lesions has been studied using some animal models such as stress or nonsteroidal antiinflammatory drug-induced gastric ulcer. Stress itself inhibits gastric acid secretion through a central nervous reflex mechanism (12). Restraint cold stress or restraint water immersion stress induces gastric lesions, which are associated with a decreased or normal level of acid secretion (13,14).…”

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confidence: 99%

A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical

Biswas¹,

Bandyopadhyay²,

Chattopadhyay³

et al. 2003

Journal of Biological Chemistry

257

199

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The mechanism of the antiulcer effect of omeprazole was studied placing emphasis on its role to block oxidative damage and apoptosis during ulceration. Dose-response studies on gastroprotection in stress and indomethacin-induced ulcer and inhibition of pylorus ligation-induced acid secretion indicate that omeprazole significantly blocks gastric lesions at lower dose (2.5 mg/kg) without inhibiting acid secretion, suggesting an independent mechanism for its antiulcer effect. Time course studies on gastroprotection and acid reduction also indicate that omeprazole almost completely blocks lesions at 1 h when acid inhibition is partial. The severity of lesions correlates well with the increased level of endogenous hydroxyl radical ( ⅐ OH), which when scavenged by dimethyl sulfoxide causes around 90% reduction of the lesions, indicating that ⅐ OH plays a major role in gastric damage. Omeprazole blocks stress-induced increased generation of ⅐ OH and associated lipid peroxidation and protein oxidation, indicating that its antioxidant role plays a major part in preventing oxidative damage. Omeprazole also prevents stress-induced DNA fragmentation, suggesting its antiapoptotic role to block cell death during ulceration. The oxidative damage of DNA by ⅐ OH generated in vitro is also protected by omeprazole or its analogue, lansoprazole. Lansoprazole when incubated in a ⅐ OH-generating system scavenges ⅐ OH to produce four oxidation products of which the major one in mass spectroscopy shows a molecular ion peak at m/z 385, which is 16 mass units higher than that of lansoprazole (m/z 369). The product shows no additional aromatic proton signal for aromatic hydroxylation in 1 H NMR. The product absorbing at 278 nm shows no alkaline shift for phenols, thereby excluding the formation of hydroxylansoprazole. The product is assigned to lansoprazole sulfone formed by the addition of one oxygen atom at the sulfur center following attack by the ⅐ OH. Thus, omeprazole plays a significant role in gastroprotection by acting as a potent antioxidant and antiapoptotic molecule.

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Inhibition of gastric acid secretion by stress: A protective reflex mediated by cerebral nitric oxide

Cited by 47 publications

References 29 publications

Immunohistochemical characterization of TH13‐L2 spinal ganglia neurons in sheep (Ovis aries)

Immunohistochemical characterization of TH13‐L2 spinal ganglia neurons in sheep (Ovis aries)

Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats

A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical

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