Involvement of prostacyclin/IP receptors in decreased acid response of damaged stomachs--mediation by somatostatin/SST2 receptors.
OBJECTIVE
We examined the effect of a prostacyclin (PGI(2)) analog iloprost on histamine-induced acid secretion and investigated how endogenous PGI(2) mediated the decreased secretory response in the damaged stomach after exposure to taurocholate (TC).


METHODS
Male C57BL/6 mice, both wild-type (WT) and IP receptor knockout (IP-KO) animals, were used after 18 h of fasting. Under urethane anesthesia, the abdomen was incised, and an acute fistula was provided in the stomach.


RESULTS
Acid secretion in WT and IP-KO mice was similarly and dose-dependently increased by histamine. Iloprost decreased the histamine-stimulated secretion in WT but not IP-KO mice. The inhibitory effect of iloprost in WT mice was totally abrogated by the prior administration of CYN154806, a selective somatostatin SST2 receptor antagonist. On the other hand, the acid secretion in WT mice was decreased after exposure of the stomach to 20 mM TC for 20 min, with an increase in mucosal PGI(2) content, but the decrease was significantly less marked in IP-KO mice. The decreased acid response to TC in WT mice was totally prevented by the prior administration of CYN154806 as well as indomethacin. Somatostatin contents in the stomach were reduced after the administration of iloprost or the mucosal exposure to TC, while the blood levels increased.


CONCLUSIONS
Somatostatin/SST2 receptors are involved in the decreased acid response of the damaged stomach, in addition to PGI(2)/IP receptors. It is assumed that PGI(2) releases somatostatin from D cells, which in turn decreases acid secretion via the activation of SST2 receptors.
Terashima
Shun
S
Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Nishio
Hikaru
H
Ogura
Michitaka
M
Honda
Maya
M
Takeuchi
Koji
K
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000502:physiology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013004:Somatostatin / Q000032:analysis / Q000097:blood; D013272:Stomach Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D013656:Taurocholic Acid
C403089:CYN 154806; D009842:Oligopeptides; C491910:Ptgir protein, mouse; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D017481:Receptors, Somatostatin; C492049:Sstr2 protein, mouse; D013004:Somatostatin; D015121:6-Ketoprostaglandin F1 alpha; D013656:Taurocholic Acid; D006632:Histamine; D016285:Iloprost