Interleukin 1 beta-induced inhibition of gastric acid secretion involves glutamate, NO and cGMP synthesis in the brain.
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 1beta on pentagastrin-stimulated acid production.The acid-inhibitory effect of central interleukin 1beta was prevented by intracisternal (i.c.) microinjections of interleukin 1beta 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 1beta. 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-1beta in the brainstem. We conclude that central glutamate receptors are involved in the acid inhibitory effect of centrally administered interleukin 1beta. This central pathway involves synthesis of NO, which acts on the enzyme sGC. However, endogenous interleukin 1beta does not seem to be involved in the inhibition of gastric acid secretion elicited by peripheral endotoxin.
García-Zaragozá
Eugenia
E
Department of Pharmacology, Faculty of Medicine, University of Valencia, Avda. Blasco Ibáñez 15, 46010 Valencia, Spain.
Hernández
Carlos
C
Barrachina
M Dolores
MD
Esplugues
Juan V
JV
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D005744:Gastric Acid / Q000378:metabolism*; D018698:Glutamic Acid / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D007375:Interleukin-1; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; D006152:Cyclic GMP