Inhibition of Gastric Acid Secretion in the Conscious Dog by the Mast-cell Stabilizing Agent, FPL 52694

The effects of the mast-cell stabilizing agent, FPL 52694, on gastric acid secretion in conscious dogs with gastric fistulae have been studied. FPL 52694 (5 or 10 mg kg-1 h-1) given intravenously during a plateau response to pentagastrin stimulation (2 micrograms kg-1 h-1) caused a maximum inhibition of acid output of about 50% but had no significant effect on volume output so that the [H+] in the juice was markedly reduced. The ratio of mucosal blood flow/acid output (Ra) was increased in the presence of FPL 52694. There was no maintained reduction of [H+] when inhibition was due to cimetidine (4 mumol kg-1, i.v.). Instillation of FPL 52694 (4.35 mg ml-1) directly into the stomach via the fistula for 30 min also resulted in an inhibition of acid output and reduction of [H+] during both pentagastrin-(2 micrograms kg-1 h-1) and histamine-stimulated (30 micrograms kg-1 h-1) secretion. Inhibition of pentagastrin-stimulated acid output by intragastric administration of FPL 52694 was much greater than the maximum effect seen following intravenous infusion. The results are discussed in relation to the possible mode of action of FPL 52694. It is concluded that FPL 52694 is active orally and has a novel action on acid secretion which may include stimulation of gastric bicarbonate secretion.