Role of histamine2 receptor in increased expression of rat gastric H(+)-K(+)-ATPase alpha-subunit induced by omeprazole.
Omeprazole is a specific inhibitor in vivo of the functioning gastric acid pump, the H(+)-K(+)-adenosinetriphosphatase (ATPase), in the secretory canaliculus of the parietal cell. It has been shown previously that omeprazole in rats led to an increase in the mRNA for the alpha-subunit of the H(+)-K(+)-ATPase. Omeprazole causes a marked increase in circulating gastrin in this species, which in turn stimulates release of histamine from the enterochromaffin-like cell. The possible role of this pathway was investigated by the in vivo administration of famotidine, a potent H2 receptor antagonist. A single intraperitoneal dose of famotidine, 200 mg/kg, produced a transient hypergastrinemia peaking at 3 h and normalizing at 12 h, inhibition of secretion that lasted for 12 h, but no change in the level of the alpha-subunit mRNA or of beta-actin mRNA. In contrast, a single dose of omeprazole, 100 mg/kg, inhibited acid secretion and produced hypergastrinemia, peaking at 12 h, both effects lasting for the 24-h observation period. Omeprazole elevated the alpha-subunit mRNA transiently by more than threefold at 3 h, with normal levels being restored at 24 h. The administration of famotidine 1 h after omeprazole did not change the effects of omeprazole on acid secretion but elevated the gastrin levels further. There was now no elevation of the alpha-subunit mRNA for the first 6 h, but a small increase at 12 h and a further increase to approximately 2.5-fold at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Tari
A
A
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Yamamoto
G
G
Sumii
K
K
Sumii
M
M
Takehara
Y
Y
Haruma
K
K
Kajiyama
G
G
Wu
V
V
Sachs
G
G
Walsh
J H
JH
D000818:Animals; D004357:Drug Synergism; D015738:Famotidine / Q000494:pharmacology; D017506:H(+)-K(+)-Exchanging ATPase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000502:physiology*; D013270:Stomach / Q000201:enzymology*
D012333:RNA, Messenger; D011970:Receptors, Histamine H2; D015738:Famotidine; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole