The Effect of Cimetidine on Basal and Stimulated Pepsin Secretion in the Isolated Whole Stomach of the Rat

1 The isolated stomach preparation of the immature rat has been used to study the stimulation and inhibition of pepsin secretion. 2 The isolated stomach secretes a basal level of pepsin. High concentrations (10(-3)M) of the H2-receptor antagonist, cimetidine, and the muscarinic receptor blocking drug, atropine, did not affect this secretion in a manner which was consistently of statistical significance. 3 Concentrations of histamine of 10(-5)M, 10(-4)M and 10(-3) M stimulated maximum levels of pepsin output of 126%, 155% and 299% respectively of control. There was no evidence that this secretion was secondary to the stimulation of acid secretion. 4 Cimetidine (10(-4)M and 10(-3)M) produced a dose-related inhibition of the pepsin output to 10(-3)M histamine, suggesting that histamine H2-receptors mediate this response. 5 Atropine (10(-3)M) had no effect on the pepsin response to 10(-3)M histamine, suggesting that muscarinic mechanisms play no part, even modulatory, in this secretion.