Effects of ranitidine on gastric vesicles containing H+,K(+)-adenosine triphosphatase in rats.
BACKGROUND
To ascertain the mechanism for rebound acid hypersecretion after treatment with an H2-receptor blocker, we investigated the effects of ranitidine on gastric H+,K(+)-adenosine triphosphatase (ATPase) in rats.


METHODS
Male Wistar rats received ranitidine (1-50 mg/kg body weight intraperitoneally twice a day for 5 days). The rats were starved for 15 h after the last treatment and then killed, and gastric vesicles containing H+,K(+)-ATPase were prepared.


RESULTS
Treatment with ranitidine dose-dependently increased protein content in the gastric vesicular fraction purified from the gastric mucosa without changing total protein content. Ranitidine also increased the content of a 94,000-dalton protein, the catalytic subunit of H+,K(+)-ATPase. On the other hand, ranitidine did not affect the specific activity of the enzyme (mumol/min/mg of the gastric vesicular protein). Since gastric vesicles in the fasting state mainly consist of the tubulovesicular membrane, these results suggest that ranidine administration increases total tubulovesicular H+,K(+)-ATPase content (mumol/min/rat) by increasing the number of tubulovesicles per parietal cell. The ranitidine-induced increase in total tubulovesicular H+,K(+)-ATPase activity was still evident 1 week after treatment and returned to control level 1 month later.


CONCLUSIONS
All these findings suggest that the increased content and total activity of tubulovesicular H+,K(+)-ATPase after ranitidine treatment may contribute to the mechanism for acid rebound after H2-blocker therapy.
Dept. of Internal Medicine (III), Asahikawa Medical College, Hokkaido, Japan.
K
K
Kubo
A
A
Uehara
T
T
Kubota
T
T
Nozu
M
M
Moriya
Y
Y
Watanabe
E
E
Shoji
S B
SB
Santos
K
K
Harada
Y
Y
Kohgo
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D002479:Inclusion Bodies / Q000187:drug effects / Q000201:enzymology; D008297:Male; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D006635:Histamine H2 Antagonists; D011899:Ranitidine; D017506:H(+)-K(+)-Exchanging ATPase