Physiology of Acid Secretion - Agents that Reduce Intragastric Acidity

AGENTS THAT REDUCE INTRAGASTRIC ACIDITY

PHYSIOLOGY OF ACID SECRETION

The parietal cell contains receptors for gastrin (CCK-B), histamine (H₂), and acetylcholine (muscarinic, M₃) (Figure 62–1). When acetylcholine (from vagal postganglionic nerves) or gastrin (released from antral G cells into the blood) bind to the parietal cell recep-tors, they cause an increase in cytosolic calcium, which in turn stimulates protein kinases that stimulate acid secretion from a H⁺/ K⁺-ATPase (the proton pump) on the canalicular surface.

In close proximity to the parietal cells are gut endocrine cells called enterochromaffin-like (ECL) cells. ECL cells also have recep-tors for gastrin and acetylcholine, which stimulate histamine release. Histamine binds to the H ₂ receptor on the parietal cell, resulting in activation of adenylyl cyclase, which increases intra-cellular cyclic adenosine monophosphate (cAMP) and activates protein kinases that stimulate acid secretion by the H⁺/K⁺-ATPase. In humans, it is believed that the major effect of gastrin upon acid secretion is mediated indirectly through the release of histamine from ECL cells rather than through direct parietal cell stimulation. In contrast, acetylcholine provides potent direct parietal cell stimulation.