Somatostatin monoclonal antibody immunoneutralization increases gastrin and gastric acid secretion in urethane-anesthetized rats.
The role of endogenous somatostatin in mediating urethane anesthesia-induced inhibition of gastric acid secretion was investigated using measurement of somatostatin messenger RNA concentrations in the antrum and the influence of somatostatin monoclonal antibody CURE.S6 on acid secretion in rats anesthetized with urethane and acutely implanted with gastric fistulas. Fifteen minutes after injection of urethane, somatostatin messenger RNA concentrations were increased by 128% compared with those in nontreated rats. The significant elevation of somatostatin messenger RNA was maintained for 2 hours after injection. Somatostatin monoclonal antibody injected intravenously (2 mg) completely reversed the inhibitory effect of somatostatin (20 micrograms/kg.h) on pentagastrin (24 micrograms/kg.h)-stimulated gastric acid secretion. The somatostatin monoclonal antibody dose dependently increased basal gastric acid secretion in urethane-anesthetized rats. Peak acid response to the somatostatin monoclonal antibody (2 mg) was observed 20 minutes after antibody injection (preinjection, 1.4 +/- 1.2 mumol/10 min; postinjection, 10.6 +/- 0.6 mumol/10 min); meanwhile, levels of plasma gastrin increased from 27 +/- 6 pg/mL to 75 +/- 8 pg/mL and were maintained elevated for the 2-hour experimental period. When gastrin monoclonal antibody 28.2 was injected together with somatostatin monoclonal antibody, the stimulatory effect of the somatostatin antibody was inhibited by 82%. A control monoclonal antibody 109-21 directed against the biologically inactive glycine-extended fragment 66-72 of progastrin did not alter basal gastric acid secretion or the inhibitory effect of somatostatin. These results indicate that one mechanism by which urethane induced low basal gastric acid secretion involved increased synthesis and release of endogenous somatostatin and associated inhibition of gastrin secretion.
Yang
H
H
Center for Ulcer Research and Education, Veterans Administration Medical Center, Los Angeles.
Wong
H
H
Wu
V
V
Walsh
J H
JH
Taché
Y
Y
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D008297:Male; D008991:Monitoring, Physiologic; D010418:Pentagastrin / Q000494:pharmacology; D011706:Pyloric Antrum / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000276:immunology / Q000502:physiology*; D014520:Urethane / Q000494:pharmacology*
D000777:Anesthetics; D000911:Antibodies, Monoclonal; D005755:Gastrins; D012333:RNA, Messenger; D014520:Urethane; D013004:Somatostatin; D010418:Pentagastrin