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, N ^G-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.