High basal gastric acid secretion in somatostatin receptor subtype 2 knockout mice.
OBJECTIVE
Somatostatin receptor subtype 2 (sst2) agonists inhibit gastric secretion. The role of sst2 in the regulation of acid secretion was assessed using sst2 knockout mice and urethane to induce somatostatin release.


METHODS
Acid secretion was monitored every 10 minutes by gastric perfusion and backtitration of perfusates in fasted, urethane-anesthetized C57/129 sst2 (-/-) mice and wild-type (+/+) mice. The ileal vein was cannulated for drug injection. Intragastric pH and serum gastrin were monitored 1 hour after anesthesia without perfusion.


RESULTS
Gastric pH values were lower in sst2 (-/-) mice (3.8 +/- 0.3) than in wild-type mice (7.1 +/- 0.1, P < 0.05), and there was no difference in gastrin levels. Basal acid output per 2 hours was 10-fold higher in sst2 knockout mice compared with wild-type mice. The gastrin antibody abolished the high basal acid secretion in sst2 (-/-) mice and had no effect in wild-type mice. The somatostatin antibody increased basal secretion by 4-fold in wild-type and had no effect in knockout mice. Somatostatin 14 or the sst2 agonist DC 32-87 inhibited pentagastrin-stimulated acid secretion in wild-type mice, but did not alter basal secretion in knockout mice.


CONCLUSIONS
These results indicate that sst2 is the main subtype whereby endogenous somatostatin suppresses gastric acid secretion through inhibition of gastrin action.
Martinez
V
V
CURE: Digestive Diseases Research Center, Veterans Administration Medical Center West Los Angeles, USA. vmartine@ceu.upv.es
Curi
A P
AP
Torkian
B
B
Schaeffer
J M
JM
Wilkinson
H A
HA
Walsh
J H
JH
Taché
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000097:blood / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics* / Q000378:metabolism*; D010418:Pentagastrin / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000819:agonists / Q000235:genetics* / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology / Q000502:physiology
D000911:Antibodies, Monoclonal; C112899:DC 32-87; D005755:Gastrins; D017481:Receptors, Somatostatin; D013004:Somatostatin; D010418:Pentagastrin