1. Factors affecting secretion of hydrochloric acid in the stomach. Mechanisms of their action.
Parietal cells, located in fundic glands of stomach, are only cells to secrete HCl, acidity of secretion can be very great, (as low as pH 0.8). However, secretion of HCl under continuous control by both endocrine & nervous signals.
Factors influencing HCL secretion
Histamine - parietal cells operate in association with enterochromaffin-like cells (ECL cells), primary function of which to secrete histamine.
ECL cells lie in fundic glands, therefore release histamine in direct contact with parietal cells. Rate of formation & secretion of HCl, by parietal cells, directly related to amount of histamine secreted by ECL cells. (Histamine has H2 receptors which coupled to adenylate cyclase via Gs. a potent stimulant of cAMP production. It activates phospohokinase A which causes activation of H+/K+ pump. thus H+ released into stomach lumen). ECL cells can be stimulated to secrete histamine in several ways: 1. Most potent mechanism for stimulation is by gastrin, formed almost entirely in antral portion of stomach mucosa in response to proteins in digested food. 2. In addition, the ECL cells can be stimulated by:
a. Acetylcholine released from stomach vagal nerve endings b. Hormonal substances secreted by enteric nervous system of stomach wall.
Direct stimulation by Acetylcholine - coming from nervus vagus binds to M3 (ACh receptors) on parietal cells membrane. M3 receptors are G proteins of class Gq which upregulate phospholipase C. phospholipase C produce second messenger molecules IP3 & DAG by hydrolysis of PIP2. IP3 binds & activates InsP3 receptor on membrane of ER & opens Ca2+ channel, resulting in release of Ca2+ into cytoplasm leading to activation of H+/K+ pump. DAG remains on the cell membrane and activates PKC. PKC activates other cytosolic proteins by phosphorylating them. effect of PKC is activation of the H+/K+ pump. Stimulation of Acid Secretion by Gastrin - Gastrin secreted by G cells, located in pyloric glands of stomach.
When protein-containing foods reach antral end of stomach, some of proteins have special stimulatory effect on gastrin cells to release gastrin into digestive juices of stomach. The vigorous mixing of gastric juices transports gastrin rapidly to ECL cells causing release of histamine directly into the deep fundic glands. histamine then acts quickly to stimulate HCl secretion.
However gastrin also directly stimulates CC KB receptors which stimulates a Gq-protein coupled receptor and has same pathway as acetylcholine, causes increase in intracellular Ca2+ and activation of H+/k+ pump to increase secretion of H+ into lumen of stomach.
Inhibiting factors
Although intestinal chyme slightly stimulates gastric secretion during early intestinal phase of stomach secretion, it paradoxically inhibits gastric secretion at other times. This inhibition results from few influences:
1. presence of food in small intestine initiates reverse enterogastric reflex that inhibits stomach secretion. This reflex can be initiated by 1)distending small bowel, 2)by presence of acid in upper intestine, 3)by presence of protein breakdown products, 4)or by irritation of mucosa. 2. presence of acid, fat, protein breakdown products, hyperosmotic or hypo-osmotic fluids, or any irritating factor in upper small intestine causes release of several intestinal hormones. One of these is secretin, which opposes stomach secretion. Three other hormone: gastric inhibitory peptide, vasoactive intestinal polypeptide, and somatostatin, also have slight to moderate effects in inhibiting gastric secretion. 3. Prostaglandins decreases gastric acid secretion through Gi inhibiting protein, this does not allow phosphorylation of the H+/K+ pump. 4. Somatostatin secreted by endocrine pancreas and hypothalamus, is also inhibitory hormone acts on somatostatin receptor on parietal cell, decreases gastric acid secretion through Gi inhibiting protein.
