Exocrine gastric secretion - SC2-E880-I

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Organic Components

Pepsinogen: protein that hydrolyzes in light, by acid pH, will give pepsin, an endopeptidase. There are class I pepsins that are produced by oxyntic mucosa cells and those of class II, produced by the gastric mucosa and the Brunner glands, in the duodenum. The optimal pH for the action of this peptidase is below 3 and the enzyme is denatured at alkaline pH. In humans, pepsinogen is produced by the main cells and stored in vesicles that, under stimulation, are released by exocytosis.

Lipase: This triglyceride hydrolyzes with short chain fatty acids.

Mucin: glycoprotein that, polymerized, forms the gel of the mucous barrier.

Intrinsic factor: the only component of essential gastric secretion. It is a protein of 55 kDa that forms with vitamin B 12     a complex resistant to the hydrolysis and that,

recognized by receptors on mucosal cells of the small intestine, is absorbed. Without this protein there is no absorption of the protein, with consequent anemia.

Electrolytic components . The major salts are NaCl and KCl. The secretion of HCl is such that the pH may be below 2.0. The concentrations of the various ions vary with the rate of secretion: with secretion at high rhythm, HCl is the main solute, and the solution tends to isotonicity with plasma. For basal rhythms of secretion, NaCl predominates as a solute and the fluid is hypotonic to the plasma. The concentration of K +, always higher than plasma, rises with the rate of secretion.

Mucosa and gastric glands . The gastric mucosa is formed by cells secreting mucin and bicarbonate. The glands are invaginations on the floor of the stomach. The cytology of the glands varies according to the region of the stomach: the mucus-secreting cells predominate in the body, in the body the pepsinogen and HCl-secreting cells and in the antrum the gas-secreting secretory mucus and endocrine cells. The neck of the gland is made up of mucus-secreting cells. In this region are still undifferentiated cells, with mitosis capacity, and which replace the lost cells. More deeply in the glands of the body region are oxyntic or parietal cells and major cells. The former secrete HCl, the latter secrete pepsinogen.

To oxyntic cells . These cells undergo tremendous structural changes when they pass from the resting state to the HCl secretion state. At rest the cytoplasm is crossed by canaliculi that open in the luminal space and the cytoplasm is replete with tubulo-vesicular structures. Stimulation promotes fusion of the vesicles with the canaliculus membrane, greatly amplifying the membrane area containing the transport systems for HCl. Fundamental for the secretion of HCl is the H + -K + pump on the apical membrane. There are still in the apical mebrana channels for K + and for Cl - . The H + secreted by the pump is supplied by the CO hydration reaction . The bicarbonate formed is exchanged in the basolateral membrane by Cl -. In the basolateral membrane there is also a Na + -K + pump and channels for K +. Both the pump Na + K + channels such as Cl -apical are modulated by cAMP - dependent kinase and Ca 2 +. The basolateral membrane there acetylcholine receptors and gastrin, intracellular signaling associated with Ca 2 + and IP . Receptors for histamine, type H , have cAMP as an intracellular flag.

The main cells . These secrete pepsinogen by exocytosis of vesicles containing it, formed in the Golgi apparatus. In the basolateral membrane there are receptors for VIP and secretin and b-adrenergic receptors that use cAMP as an intracellular messenger. Receptors for acetylcholine and for gastrin and CCK mobilize the cascade of DAG and IP .

The mucus secreting cells of the gastric surface. These cells secrete mucin and bicarbonate. Mucin is a glycoprotein, with the peptide backbone rich in serine, threonine and tyrosine. Hydroxyls of these residues are linked by ester linkages to galactose sugars and N-acetylglucosamine. The binding of sugars protects the peptide chain from enzymatic hydrolysis. Peptide chain terminations are rich in cysteines, and disulfide bonds may pool the molecules in a tetramer, which, at suitable concentrations, forms a gel. The gel covers the mucosa. As this is also bicarbonate, the gel restricts the movement of bicarbonate to light and H + from light to the surface of the cell, pH in the gel layer from luminal acidity to a relatively alkaline value on the surface of the cells. As the junction of the 4 molecules undergoes pepsin attack, the mucin has to be continuously secreted for the preservation of the mucus layer. Stimulants of mucus secretion, such as ACh and Ca2 + reinforce the protective layer. Secretion inhibitors, such as α-adrenergic agonists, aspirin and non-steroidal anti-inflammatory drugs, place the mucosa at risk of aggression by acid pH and pepsin.

Control of secretion in parietal cells . There are, on the basolateral membrane of these cells, cholinergic receptors for ACh released by the neuron terminations of the enteric ganglia. These receptors trigger the DAG and IP cascade . There are also receptors for gastrin, a hormone released by the G cells of the mucosa of the antrum. These receivers also use DAG and IP 3as intracellular messengers. The stimuli for the release of gastrin are the cholinergic action of the neuron terminations of the enteric ganglia, the most alkaline pH of the stomach lumen, peptides and amino acids of the chyme. Both cholinergic neurons and gastrin stimulate the release of histamine by enterocromoafins (ECL) cells. Histamine stimulates HCl secretion by H2 receptors, blocked by cimetidine, for example, use cAMP as an intracellular messenger. There are endogenous inhibitors of HCl secretion, which, when binding to the respective receptors, activate a G1 protein, adenylate cyclase inhibitor and, therefore, the cellular production of cAMP. Somatostatin, prostaglandins E and I, and epidermal growth factor (EGF) thus act.

Control of the secretion of pepsinogen by the main cells . Secretion in these cells is stimulated by VIP and secretin and by b-adrenergic action. Both types of receptors raise the cellular production of cAMP. ACh, acting on M3 receptor, and Gastrin and CCK, binding to the common receptor, stimulate secretion by activating the DAG and IP cascade .

Phases of gastric secretion control .

a- Cephalic phase: The gustatory, visual and olfactory stimuli trigger the reflex, which uses the vagus to stimulate the various pathways that at the mucosal level lead to the production of secretion. There are several areas in the CNS operating in secretion control. Certainly in the hypothalamus there are of these areas. This phase was studied with the collection of gastric secretion in animals with esophageal fistula.

b- Gastric phase. The stimuli for the reflex are mechanical (distension) and chemical (pH, amino acids, peptides, Ca 2+ ). The receptors are neurons that integrate local or long reflex arches, covering the CNS, or the endrocrine cells themselves, in the case the gastrin producing Gs. The stimulus to secretion is given by cholinergic neurons, gastrin and histamine.

c- Intestinal phase. The entry of food into the duodenum leads, through neural and endocrine circuits, to the modification of the motor and secretory activity of the stomach. Peptides and amino acids in the duodenum stimulate the release of gastrin and oxintine, which increase gastric motility and secretion. If the pH of chyme penetrating the duodenum is less than 5, there is release of secretin and GIP which, by inhibiting the release of gastrin, reduces gastric secretion. Fats stimulate the duodenum to secrete CCK which, being a poorly potent agonist for the gastrin receptor, inhibits its action. Another inhibitory hormone, still chemically unknown, is bulbogastrone.

Guiding questions of the study.

a- Discuss the main components of gastric secretion, concentrations in relation to the rate of growth. Discuss the cellular mechanisms of secretion. Discuss the mucosal barrier in its dynamics, function and the consequences of its dissolution.

b- Discuss the composition of the gastric secretion and the mechanisms of its control in an animal that is fed after esophageal fistula. What effect would vagotomy have on secretion? Discuss the control in the gastric secretion with the food in the stomach and after the arrival of the chyme also in the duodenum. Analyze the physiological importance of intestinal control of gastric motility and secretion.

Discuss how cimetidine blocks gastric secretion. What clinical uses will this substance have?

 

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