INVOLVEMENT OF NEURONAL PROCESSES AND NITRIC-OXIDE IN THE INHIBITION BY ENDOTOXIN OF PENTAGASTRIN-STIMULATED GASTRIC-ACID SECRETION

Administration of E. coli endotoxin (1 mg kg(-1), i.v.) abolished the acid response induced by the i.v. infusion of pentagastrin (8 mu g kg(-1) h(-1)) in the continuously perfused stomach of the anaesthetized rat. Local serosal application of tetrodotoxin (36 ng per rat) completely restored acid responses to pentagastrin in endotoxin-treated rats. However, pretreatment with atropine (0.5 mg kg(-1), s.c.), capsaicin (20, 30, and 50 mg kg(-1), s.c. 2 weeks before the study) or guanethidine (16 mg kg(-1), s.c. 3 and 16h before) did not influence the inhibitory effects of endotoxin. Continuous i.v. infusion with N-G-nitro arginine methyl ester (L-NAME, 10 mg kg(-1) h(-1)) restored the secretory responses to pentagastrin in endotoxin treated rats. The effects of L-NAME were reversed by L-arginine (100 mg kg(-1) h(-1) i.v.), but not by its enantiomer D-arginine (100 mg kg(-1) h(-1), i.v.). The secretory responses elicited by pentagastrin (10(-10)-10(-6) M) in the isolated lumen perfused stomach of the rat were not influenced by incubation (100 min) with endotoxin (10 mu g ml(-1)). These observations with tetrodotoxin indicate that inhibition of acid secretion by endotoxin in vivo involves neuronal activity, while inhibition of NO synthesis had a comparable inhibitory action. Activation of a systemic non-adrenergic non-cholinergic neuronal pathway involving NO could thus mediate the acute acid inhibitory effects of endotoxin.