Acetylcholine stimulates acid secretion

The histamine H2-receptor (359 amino acids) is best known for its effect on gastric acid secretion. Histamine H2-receptor activation, in conjunction with gastrin and acetylcholine from the vagus, potently stimulate acid secretion from parietal cells. High concentrations of histamine are also present in cardiac tissues and can stimulate positive chronotropic and inotropic effects via H2-receptor stimulation and activation of adenylyl... 

The parietal cell contains receptors for gastrin, histamine (H2), and acetylcholine (muscarinic, M3) (Figure 63-1). When acetylcholine or gastrin bind to the parietal cell receptors, 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 have receptors for gastrin and acetylcholine and are the major source for histamine release. Histamine binds to the H2 receptor on the parietal cell, resulting in activation of adenylyl cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP). cAMP 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. 

G. is formed in the antrum mucosa in response to alkaline pH, mechanical stimulation and vagus (acetylcholine) stimulation. Acidic stomach juice inhibits its secretion. The presence of G. in the blood stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. Cholecystokinin is a competitive inhibitor of G. 

The basal rate of proton secretion is around 10% of maximal but the perception of food (smell, taste, sight or even just the thought of it) increases secretion. This is the cephalic effect of food. Nervons signals from the brain canse release of acetylcholine, histamine and gastrin to stimnlate acid secretion from the parietal cells. When food actnally reaches the stomach, distension, proteins, peptides and amino acids farther stimulate the release of gastrin. 

The gastric acid secretion can be stimulated by the transmitters acetylcholine, histamine and the hormone gastrin. Histamine, acting via H2-receptors,... 

Aihaara T et al Cholinergically stimulated gastric acid secretion is mediated by M3 and M5 but not Mi muscarinic acetylcholine receptors in mice. Am J Physiol 2005 288 G1199. 

As the H+ is pumped into the lumen of the stomach, HC03 moves out of parietal cells into blood and Cl- enters the cell in exchange. Acid secretion is stimulated by histamine acting on H2 receptors, by acetylcholine acting on muscarinic (Ml) receptors and by gastrin acting on gastrin receptors of the parietal cells. 

Parietal cells possess receptors for three stimulators of acid secretion neural (acetylcholine, muscarinic-type receptor), paracrine (gastrin) and endocrine control (histamine, H2 type receptor) (Figure 4.2). 

Werner (W9) found 3.0% sialic acid in dog gastric juice, as compared with 14.4% hexosamine, 3.7% hexuronic acid, and 3.0% fucose per dry weight of nondialyzable gastric solids. Chromatographic analysis showed hexosamine, galactose, and fucose. Anacid canine gastric secretion after acetylcholine stimulation (H43-H45) showed a sialic acid to hexosamine ratio of 0.07 and sialic acid to fucose ratio of 0.2, the acid gastric secretion 0.12 and 0.5, respectively. 

Gastric acid is secreted by the parietal cells in gastric mucosa. The basolateral membranes of these cells contain receptors for the three main stimulants of acid secretion, namely gastrin (from antral G cells), histamine (from enterochromaffin-Uke cells) and acetylcholine (from vagal efferents). The action... 

The presence of food in the stomach evokes gastric secretion. The principal stimuli include distension of the stomach and the presence of amino acids and peptides. Distension of the stomach stimulates mechanor-eceptors that bring about secretion of acetylcholine, hydrochloric acid, and gastrin. 

Hie final step in acid secretion in the parietal cell is the extrusion ( pumping") of prottms. The membrane pump, an H /K -ATPase. catalyzes the exchange of hydrogen ions for potassium ions. Inhibition of this proton pump acts beyond the site of action of second messengers (e.g.. Ca and cAMP) and is independent of the action of secretogogues histamine, gastrin, and acetylcholine. Thus, acid pump inhibitors block basal and stimulated secretion. 

The mechanism of acid secretion is stiU widely debated there is, however, significant agreement that acetylcholine, histamine, and gastrin act through their respective neuro-crine, paracrine, and endocrine pathways to stimulate the parietal cells, and that specific parietal cell receptors to these transmitters exist. Also, there are potentiating interactions between the mentioned secretagogues that probably occur at the parietal ceil itself. Histamine has a role as a mediator or a potentiator of the actions of other secretagogues. Admin-... 

Schematic representation of the resting (left side) and stimulated (right side) state of the parietal cell. Basolateral membrane contains three major receptor classes gastrin (G), acetylcholine (ACh), and histamine (H). Their actions are mediated by cAMP responses, Ca changes, or both. In addition, there are a number of ion transport pathways. In the stimulated state, the apical membrane acquires H", K -ATPase contained in the tubulovesicles (tv) as well as the property of K+ and CI conductance, both of which are essential in the secretion of HCl. A change in cytoskeletal arrangement is also associated with stimulation. CaM = calmodulin SC -secretory canaliculus mf = microfilaments. [Reproduced with permission from D. H. Malinowska and G. Sachs, Cellular mechanisms of acid secretion, Clin. Gastroenterol. 13, 322 (1984).]...

H2 receptor antagonists are extremely effective inhibitors of acid secretion during pentagastrin stimulation and are able to inhibit partially the secretion due to vagal stimulation. Since neither gastrin nor acetylcholine binds to H2 receptor, it is apparent that histamine must therefore operate on the pathway of stimulation initiated by these mediators. Thus it seems likely that histamine rather than gastrin is the final mediator of acid secretion. 

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