Effects of common inhibitors of gastric acid secretion on secretagogue-induced respiration and aminopyrine accumulation in isolated gastric glands.

1. The effects of three inhibitors of gastric acid secretion, atropine, burimamide and thiocyanate, have been studied in isolated glands from the rabbit gastric mucosa. The glands were either resting or stimulated by carbachol, histamine or dibutyryl cyclic AMP. The effects were determined from changes in oxygen consumption and accumulation of the weak base aminopyrine. The latter gives an indirect measurement of the acid production in the glands. 2. Atropine (10 (-6) M) almost totally inhibited the transient response induced by carbachol (10 (-4) M) in both measured parameters. The histamine-induced increase in respiration was inhibited when the atropine concentration was raised to 10 (-4) M. To a lesser extent also, histamine-induced aminopyrine accumulation was reduced. The dibutyryl cyclic AMP stimulated oxygen consumption was not affected by atropine. 3. Burimamide competitively inhibited the histamine responses but was without effect on those of carbachol and dibutyryl cyclic AMP. 4. Thiocyanate (10 (-2) M) inhibited the increase in oxygen consumption induced by all three secretagogues but not down the prestimulatory level, in spite of total abolishment of the aminopyrine accumulation. 5. In unstimulated glands, burimamide (10 (-3) M) or atropine (10 (-4) M) did not alter the normal aminopyrine ratio (aminopyrine in intraglandular water/ aminopyrine in extraglandular water) of approximately 50. This may indicate the existence of preformed acid in resting parietal cells. Thiocyanate, on the other hand, lowered the aminopyrine ratio in unstimulated glands from 46 to 2. Possible mechanisms for the thiocyanate effect are discussed in terms of an inability to separate acid and base in the secreting membrane.