Regulation of gastric acid secretion at the cellular level.
Gastric acid secretion is controlled by neurocrine, endocrine, and paracrine pathways. At the organ level, the neurocrine and endocrine systems provide long-range regulation; and near the target cell the paracrine system appears to predominate. The integration of the regulatory commands from these various pathways is complex and, as a result, some pathways have not yet been clearly defined. Present evidence suggests that acetylcholine from mucosal nerve endings acts by 2 possible pathways. It interacts with muscarinic receptors on the oxyntic cell stimulating acid production. It is also capable of releasing histamine from the paracrine cell in the gastric glands, and histamine then acts on the oxyntic cells. The endocrine effect on acid secretion mediated by gastrin is less clear. Gastrin binds to oxyntic cell plasma membranes but has little or no direct stimulatory effect on the acid-secreting cell. It is assumed that its stimulatory action on acid secretion in vivo is mediated primarily by increasing histamine levels near the oxyntic cells. Histamine, released from paracrine cells near the oxyntic cells, is probably controlled by acetylcholine and gastrin, but other mechanisms are being explored. Histamine binds to the H2-receptors on the oxyntic cell plasma membrane, activating adenylate cyclase, which catalyzes the production of the intracellular messenger cyclic AMP. Cyclic AMP in turn activates a specific protein kinase, which phosphorylates a yet unknown substrate for the propagation of the stimulatory signal. The action of acetylcholine on the oxyntic cell receptors does not stimulate the production of cyclic AMP; instead, it acts on Ca++ channels, increasing the Ca++ entrance into the cell, which initiates the intracellular events.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000294:innervation; D005755:Gastrins / Q000502:physiology; D006632:Histamine / Q000502:physiology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011970:Receptors, Histamine H2 / Q000502:physiology
D005755:Gastrins; D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; D006632:Histamine; D000242:Cyclic AMP; D000109:Acetylcholine; D002118:Calcium