Effects of drugs influencing gastric secretion on the quantitative histological distribution of cyclic adenosine 3':5'-monophosphate in the rat stomach.

To help clarify conflicting evidence on the cyclic adenosine 3':5'-monophosphate (cyclic AMP) role in acid secretion in the rat stomach, and to establish the quantitative effects on cyclic AMP concentrations in histological regions of the glandular stomach of the 24-hr fasted rat of injections of drugs that stimulate or inhibit gastric secretion, the concentrations were measured by the firefly luminescence method using fresh-frozen microtome tissue sections cut serially through the stomach wall. The data are compatible with cyclic AMP involvement in the acid secretion. Parietal-mucous neck cell cyclic AMP levels (3.3,0.11 means, expressed as picomoles per mg of wet weight and picomoles per mug of protein-nitrogen, respectively) were the highest in any region. Pentagastrin or urecholine elevated these values slightly, and theophylline produced greater increases in all regions (parietal-mucous neck cell, 5.4, 0.22), but theophylline administered either with pentagastrin or urecholine further elevated the values (8.3, 0.31). Urecholine or pentagastrin plus theophylline each generated two approximately equal cyclic AMP concentration peaks (about one-half parietalmucous neck cell concentrations (2.7, 0.22), perhaps by negative feedback, but low dose (2 mg per kg) elevated these values more than pentagastrin or urecholine, and with theophylline they were greatly increased (9.1, 0.32). The inhibitors, atropine and prostaglandin E2, alone or with theophylline, had little influence on parietal-mucous neck cell cyclic AMP levels but caused an increase in chief cell and muscle zones.