Lack of interaction between acid and pepsinogen secretion in isolated gastric glands

Gastric glands isolated from rabbit stomach were employed to study the relation between acid and pepsinogen secretion. The effects of adenosine and guanosine nucleotides were examined for both secretory processes. cAMP, dibutyryl cAMP (DBcAMP), and 8-bromo-cAMP (8BrcAMP) were found to stimulate both acid and pepsinogen secretion with a potency sequence of 8BrcAMP greater than DBcAMP greater than cAMP. Adenosine, ATP, and AMP were ineffective, indicating that the responses to adenosine cyclic nucleotides do not involve an adenosine receptor. 8BrcGMP was found to produce a weak stimulation of both acid and pepsinogen secretions, while GMP, cGMP, and DBcGMP were ineffective. DBcGMP was found to inhibit competitively the stimulation of pepsinogen secretion by cholecystokinin (CCK)-like peptides. No inhibition was found with cGMP or 8BrcGMP. Stimulation of pepsinogen secretion by carbachol or isoproterenol was not inhibited by DBcGMP nor was the stimulation of acid formation by CCK-like peptides. Thiocyanate inhibited acid formation but did not affect pepsinogen secretion stimulated by 8BrcAMP or carbachol, indicating that stimulation of pepsinogen secretion does not require simultaneous acid formation. Costimulation of acid formation by histamine and pepsinogen secretion by isoproterenol showed no interaction between the two secretory processes. The results are interpreted to suggest that correlations between acid and pepsinogen secretion observed in vivo do not result from direct interactions between parietal and chief cells.