Effects of topical application of KT1-32 on transmucosal potential difference and acid secretion in the rat stomach.
Effects of intragastric application of azuletil sodium (KT1-32), a novel antiulcer drug, on transmucosal potential difference (PD) and acid secretion were investigated in the rat stomach. The stomach was mounted on a Lucite chamber and perfused with saline before and after exposure to KT1-32 for 10 min. KT1-32 (3-30 mg/kg) produced an elevation of PD in a dose-dependent manner with a rise of the luminal pH. The increased PD response caused by KT1-32 (10 mg/kg) persisted after removal of the agent from the stomach, but this PD generating effect was significantly mitigated by pretreatment with omeprazole (60 mg/kg, i.p.). KT1-32 raised PD under basal conditions, but did not significantly affect the reduced PD response caused by 30% ethanol. In addition, topical application of KT1-32 significantly reduced acid secretion caused by histamine (4 mg/kg/hr, i.v.) and carbachol (20 micrograms/kg/hr, i.v.). In the in vitro study, KT1-32 at 3.9 x 10(-4) M showed 50% inhibition of the H/K ATPase activity prepared from the hog gastric mucosa. These results suggest that KT1-32 exerts locally antisecretory and PD generating effects. The latter may be accounted for by the antisecretory action, which is probably related to the H/K ATPase inhibition.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Tanaka
T
T
Wakabayashi
S
S
Mochizuki
S
S
Tomiyama
A
A
Okabe
S
S
D000287:Administration, Topical; D000818:Animals; D052176:Azulenes; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D052176:Azulenes; D012717:Sesquiterpenes; D000431:Ethanol; D006632:Histamine; C061956:azuletil; D009853:Omeprazole