At a cellular level, the major stimulant(s) of acid secretion by the gastric parietal cell is/are:

a. Histamine

c. Acetylcholine

d. Gastrin

The three major stimulants of acid secretion by the parietal cell are acetylcholine, gastrin, and histamine. Acetylcholine is released from cholinergic nerve endings in close proximity to parietal cells and binds to muscarinic receptors. Cholinergic stimulation of parietal cells is coupled to hydrolysis of membrane-associated lipids (termed phosphatidylinositides) and leads to increases in intracellular calcium. Histamine is released from mast cells in the lamina propria and reaches parietal cells by diffusion. Histamine occupies H2 receptors that may be selectively blocked by agents such as cimetidine. Histamine stimulation of parietal cell acid secretion is mediated by a cyclic AMP-dependent pathway. Gastrin is delivered to the fundic mucosa by the systemic circulation from its source in the antrum and duodenum. Like acetylcholine, gastrin causes increases in membrane phosphoinositol turnover and increases intracellular calcium.

Activation of parietal cells by acetylcholine, gastrin or histamine can be blocked by somatostatin. Local release of somatostatin is physiologically important in modulating postprandial gastric acid secretion. Prostaglandin E2 and its synthetic derivatives are potent inhibitors of histamine-stimulated acid secretion.