Dolores Barrachina

Nitric oxide donors preferentially inhibit neuronally mediated rat gastric acid secretion

Continuous i.v. infusion of the nitric oxide (NO) donors, S-nitroso-glutathione (10-50 micrograms kg-1 min-1) and S-nitroso-N-acetyl-penicillamine (10 micrograms kg-1 min-1) inhibited neuronally mediated gastric acid secretion, as induced by gastric distension (20 cm water) or i.v. bolus administration of 2-deoxy-D-glucose (150 mg kg-1) in the anaesthetized rat. By contrast, gastric acid responses to i.v. infusion of submaximal doses of pentagastrin (8 micrograms kg-1 h-1) or histamine (1 mg kg-1 h-1) were not influenced by these NO donors. These findings suggest that NO does not directly influence acid secretion in vivo but could play an inhibitory modulator role in neuronally mediated acid responses.

Interleukin 1β-induced inhibition of gastric acid secretion involves glutamate, NO and cGMP synthesis in the brain

Abstract. This study examines the role of a central pathway involving glutamate receptors, nitric oxide (NO) and cGMP in the acute inhibitory effects of central interleukin 1β on pentagastrin-stimulated acid production.The acid-inhibitory effect of central interleukin 1β was prevented by intracisternal (i.c.) microinjections of interleukin 1β together with the NMDA receptor antagonist, dizocilpine maleate (MK-801). Intracisternal co-administration of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME) or 1H-[1,2,4]oxazodiolo[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase (sGC) blocker, both reversed the hyposecretory effect of central interleukin 1β. Peripheral administration of endotoxin significantly reduced pentagastrin-stimulated gastric acid secretion. I.c. pre-treatment with the interleukin 1 receptor antagonist, IL-1ra, failed to restore acid secretory responses in these rats. In addition, endotoxin did not modify the levels of endogenous mRNA for IL-1β in the brainstem.We conclude that central glutamate receptors are involved in the acid inhibitory effect of centrally administered interleukin 1β. This central pathway involves synthesis of NO, which acts on the enzyme sGC. However, endogenous interleukin 1β does not seem to be involved in the inhibition of gastric acid secretion elicited by peripheral endotoxin.

Effects of endotoxin on neurally-mediated gastric acid secretion in the rat

The effects of a peripheral administration of E. coli endotoxin on neurally‐mediated gastric acid secretion and the role of endogenous opioids or PAF receptors in endotoxin effects have been evaluated in the continuously perfused stomach of the anaesthetized rat.

T1967 iNOs-Derived No Mediates TFF2 Expression in the Damaged Mucosa of Aspirin-Treated Rats

Trefoil peptides are involved in mechanisms of defense and repair in the gastrointestinal tract. We have recently demonstrated a HIF-1 dependent induction of TFF genes by hypoxia in gastric epithelial cells but less is known about TFF genes regulation In Vivo. Nitric oxide has been shown to modulate HIF-1 activity in cellular models. AIM: To analyze the role of iNOS-derived NO on HIF-1α stabilization and the TFF2 mRNA expression in the damaged mucosa of aspirin-treated rats. MATERIALM b) significantly reduced the increase in TFF2 mRNA expression observed 3 and 6 h after aspirin administration, and delayed the fall of TFF2 mRNA expression at 24h; c) diminished HIF-1α immunostaining. CONCLUSIONS: iNOS-derived NO induces HIF-1α stabilization and TFF2 mRNA expression in the damaged mucosa of aspirin-treated rats. These results suggest that iNOS-derived NO may contribute to the recovery of the gastric mucosa by modulating the epithelial gene expression.