Involvement of vagal pathway in the anti-secretory effect of a novel xanthine derivative.
The inhibitory action of a novel xanthine derivative, 3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine (A90 6119) on gastric acid secretion was studied in rats. In conscious pylorus-ligated rats, A90 6119 (3 mg/kg intraduodenally, i.d.), inhibited gastric acid output stimulated by carbachol and by 2-deoxy-D-glucose by 49% and 100% respectively. Basal acid secretion was inhibited by 61% by 10 mg/kg, i.d. A90 6119. In urethane anesthetized stomach-lumen-perfused rats, A 90 6119 at 1 and 3 mg/kg, i.d. significantly reduced the acid secretion stimulated by 2-deoxy-D-glucose, by 83% and 100%, respectively. The stable thyrotropin-releasing hormone (TRH) analog, RX 77368, injected intracisternally (i.c.) at a 30 ng dose, induced concomitant increases in acid secretion and gastric mucosal blood flow. A90 6119 (10 micrograms/rat, i.c.) inhibited by 93% and 132% the increase in acid secretion and gastric mucosal blood flow induced by i.c. injection of TRH analog, respectively. These data suggest that the anti-secretory effect of A90 6119 involves inhibition of both central and peripheral vagal cholinergic pathways.
Tanaka
T
T
Laboratory for Pharmacology, Hoechst Japan Ltd., Saitama, Japan.
Taché
Y
Y
Guth
P H
PH
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D014970:Xanthines; C082076:3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D003847:Deoxyglucose; D011761:Pyrrolidonecarboxylic Acid