EFFECT OF CIMETIDINE ON STIMULATED GASTRIC-SECRETION AND SERUM GASTRIN IN THE DOG

  • 1 January 1978
    • journal article
    • research article
    • Vol. 70  (5) , 437-447
Abstract
The histamine H-2 receptor antagonist cimetidine was given for 90 min to 4 fistula dogs during a steady dose 270-min infusion of histamine (50 .mu.g base/kg h), urecholine (80 .mu.g/kg h) or pentagastrin (1.5 .mu.g/kg h). In each case there was gradual but marked (75-95%) inhibition of acid secretion with maximal effects after 60-90 min while pepsin secretion was also suppressed but to a lesser extent. These effects persisted for at least the 90 min after the end of cimetidine infusion. Serum gastrin was not significantly changed by cimetidine. Kinetics of effect of cimetidine were derived from step-dose responses to histamine (2-150 .mu.g/kg h), pentagastrin (0.1 to 10 .mu.g/kg per h) and urecholine 20-160 .mu.g/kg per h) which were made alone and with background infusions of cimetidine. Cimetidine acted competitively for acid output with histamine as the stimulus and noncompetitively for pentagastrin or urecholine. With histamine or pentagastrin pepsin was less inhibited than H+ and in the case of urecholine, pepsin secretion was not inhibited by cimetidine. Cimetidine is effective against all stimuli acting on the parietal cell to secrete acid, though the mechanism of this effect is unknown for the non-histamine stimuli. It is far less effective against agents which stimulate pepsin secretion. In the case of histamine, cimetidine blocks an action of histamine which, at high doses, inhibits pepsin secretion.