[New target for the inhibitors of gastric acid secretion. Inhibition of myosin and actin activities via the apical membrane of parietal cells in dogs].
This report aims to highlight drugs that are able to inhibit parietal cells from the luminal side, resulting in suppressed gastric acid secretion. Histamine 2HCl was i.v. given continuously to obtain a submaximal stimulation of gastric acid secretion. Wortmannin and ME 3407 (a myosin light chain kinase inhibitor) and cytocharasin D (actin polymerizing inhibitor) were locally applied to denervated gastric pouches prepared in dogs for 5 to 30 min. Each drug, administered 0.5 hr before or 1 hr after histamine infusion was commenced, significantly inhibited stimulated-gastric acid secretion in a time-dependent manner. The antisecretory effect persisted for more than 24 hrs in the case of Wortmannin and 9 hr in the case of ME 3407 at a dosage 1 and 3 mg/pouch for 30 min, respectively. ME 2407, however, had no antisecretory effect when i.v. administered after histamine infusion, or orally administered before histamine infusion. Such results strongly suggest that the apical membrane of parietal cells possesses a ME 4307, Wortmannin and cytocharasin D sensitive portion similar to the basolateral membrane that usually mediates gastric acid secretion. The apical membrane represents an intriguing target for developing new antisecretory drugs, as well as for elucidating the functional features of parietal cells.
Okabe
Susumu
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
Fujishita
Teruaki
T
Jinbo
Keisuke
K
D000199:Actins / Q000037:antagonists & inhibitors*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015638:Cytochalasin D / Q000494:pharmacology; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D009218:Myosins / Q000037:antagonists & inhibitors*; D010295:Parietal Cells, Gastric / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D000077191:Wortmannin
D000199:Actins; D000730:Androstadienes; C106473:ME 3407; D011725:Pyridines; D013844:Thiazoles; D015638:Cytochalasin D; D009218:Myosins; D000077191:Wortmannin