Selective action of a CCK-B/gastrin receptor antagonist, S-0509, on pentagastrin-, peptone meal- and beer-stimulated gastric acid secretion in dogs.
BACKGROUND
The pharmacological effects of a novel CCK-B/gastrin receptor antagonist, S-0509, on gastric acid secretion in dogs remain unknown.


OBJECTIVE
To evaluate the antisecretory effects of S-0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants.


METHODS
Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer.


RESULTS
In the Heidenhain pouch model, both intravenously administered and orally administered S-0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol-stimulated or histamine-stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non-selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S-0509 significantly inhibited pentagastrin-stimulated gastric acid secretion, yet the drug had no effect on carbachol-stimulated secretion.


CONCLUSIONS
S-0509 is a selective CCK-B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin-releasing substances, but does not inhibit histamine-stimulated and carbachol-stimulated acid secretion.
Sasaki
N
N
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
Matsuno
K
K
Okabe
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001515:Beer; D001577:Benzophenones / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology*; D010461:Peptones / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D001577:Benzophenones; D010461:Peptones; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C109118:S 0509; D001285:Atropine; D006632:Histamine; D002217:Carbachol; D010418:Pentagastrin