Intracisternal neutral endopeptidase-24.11 inhibitors produce inhibition in gastric acid output: independence from opiate, bombesin, or neurotensin-mediated mechanisms.
Intracisternal (ic) injection of the neutral endopeptidase-24.11 inhibitor phosphoramidon (1-100 nmol) produced a dose-dependent inhibition of gastric acid secretion in 2-h pylorus-ligated rats. The response resulted from a reduction in acid concentration and volume. Likewise, ic injection of another neutral endopeptidase-24.11 inhibitor Zincov (200 nmol) produced a 63% inhibition in gastric acid output. In contrast, neither intravenous injection of phosphoramidon (100 nmol) nor ic injection of the aminopeptidase inhibitor amastatin (100 nmol) produced any change in gastric acid secretion. The inhibitory effect of ic phosphoramidon (10 nmol) was not reversed by a dose of naloxone sufficient to antagonize the acid inhibitory effects of ic [D-Ala2-D-met5]enkephalinamide (8.5 nmol). Moreover, phosphoramidon-induced inhibition of acid was not reduced by the centrally effective bombesin antagonist N-acetyl-GRP(20-26)-O-CH3 or by reserpine pretreatment at a dose effective to antagonize ic neurotensin-induced inhibition in acid secretion. These results suggest that an endogenous neutral endopeptidase-24.11 sensitive substrate may act in the brain to inhibit gastric acid output by mechanisms independent of CNS opiate, bombesin or neurotensin activity.
Stephens
R L
RL
Ohio State University, Department of Physiology, College of Medicine, Columbus 43210.
LePard
K J
KJ
Mohammed
J R
JR
Ward
P E
PE
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D006020:Glycopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology
D000900:Anti-Bacterial Agents; C071104:GRP, N-acetyl (20-26) methyl ester-; D005768:Gastrointestinal Hormones; D006020:Glycopeptides; D006877:Hydroxamic Acids; D009842:Oligopeptides; D010455:Peptides; D009270:Naloxone; C016977:amastatin; C048727:zincov; D012110:Reserpine; D015260:Neprilysin; C008890:phosphoramidon