The binding of acetylcholine to M3 muscarinic receptors opens Ca++ channels in the apical plasma membrane, while also promoting the release of Ca++ from intracellular stores, resulting in elevated intracellular [Ca++]. This leads to an increase in H+ secretion by activating basolateral K+ channels and causing the insertion of more H+,K+-ATPase molecules and Cl− channels into the apical plasma membrane. Gastrin enhances acid secretion by binding to CCK2 receptors.

In the stomach, some digestion of nutrients occurs, although it is not necessary for complete digestion of a meal as intestinal digestion is sufficient. The stomach does facilitate some amylase-mediated digestion of carbohydrates, even though amylase is typically inactivated at low pH. This is because carbohydrate protects the enzyme from degradation when it occupies the active site of amylase.

Vagal parasympathetic stimulation of gastric secretions occurs through enteric neurons. Vagal preganglionic neurons innervate the myenteric and submucosal plexus, affecting various functions. Acetylcholine (ACh) and gastrin-releasing peptide (GRP) are involved in this process.

The mechanism of action of agonists (secretagogues) and antagonists that regulate secretion in parietal cells involves various signaling pathways. Acetylcholine binds to muscarinic M3 receptors, histamine acts via H2 receptors, and gastrin binds to the cholecystokinin type 2 (CCK2) receptor. These receptor activations lead to the opening of Ca++ channels and release of Ca++ from intracellular stores, increasing cytosolic [Ca++] levels. H2 receptors also activate adenylyl cyclase to raise intracellular levels of cAMP. Other molecules and pathways, such as adenylyl cyclase, diacylglycerol (DAG), inositol triphosphate (IP3), protein kinase C (PKC), and transforming growth factor α (TGF-α), are also involved in the signal transduction mechanisms.

While digestion of lipids does start in the stomach, the extent of hydrolysis of triglyceride is approximately 10%, and it is not necessary for normal digestion and absorption of dietary lipids. The mixing patterns of gastric motility result in the formation of an emulsion of lipids and gastric lipase, which generates free fatty acids and monoglyceride from dietary triglyceride. However, due to the low luminal pH in the stomach, the products of lipolysis are not available for absorption.

The surface of the stomach is protected from the effects of H+ and pepsins by mucus and HCO3−. The gastric mucosal barrier, formed by a protective mucus gel and alkaline secretions within it, prevents damage to the stomach's mucosa by gastric contents.
Fig. 29.4 ). Acetylcholine binds to M3 muscarinic receptors and opens Ca++ channels in the apical plasma membrane. Acetylcholine also elevates intracellular [Ca++] by promoting release of Ca++ from intracellular stores, which enhances H+ secretion by activating basolateral K+ channels and causing more H+,K+-ATPase molecules and Cl− channels to be inserted into the apical plasma membrane. Gastrin enhances acid secretion by binding to CCK2 receptors (Fig. 29.10
Digestion in the Stomach
Some digestion of nutrients occurs in the stomach. However, this is not required for full digestion of a meal; intestinal digestion is sufficient. Some amylase-mediated digestion of carbohydrates occurs in the stomach. Amylase is sensitive to pH and inactivated at low pH; however, some amylase is active even in the acidic gastric environment of the stomach because of substrate protection. Thus when carbohydrate occupies the active site of amylase, it protects the enzyme from degradation.
• Fig.29.9Vagal parasympathetic stimulation of gastric secretions via enteric neurons. Vagal preganglionic neurons innervate the myenteric and submucosal plexus. The terminals of the vagal preganglionic neurons innervate many enteric neurons and thus bring about changes in function as described in
Fig.
29.7 . ACh, acetylcholine; GRP, gastrin-releasing peptide.
• Fig.29.10Signal transduction mechanisms showing the mechanism of action of agonists (secretagogues) and antagonists that regulate secretion in parietal cells. Acetylcholine (ACh) binds to muscarinic M3 receptors. Histamine acts via the H2 receptor. Gastrin binds to the cholecystokinin type 2 (CCK2) receptor. Activation of M3 and CCK2 receptors results in opening of Ca++ channels and release of Ca++ from intracellular stores and thus an increase in cytosolic [Ca++]. Activation of H2 receptors activates adenylyl cyclase to increase intracellular levels of cAMP. Ac, adenylyl cyclase; ACh, acetylcholine; CCK, cholecystokinin; DAG, diacylglycerol; EGF, epidermal growth factor; IP3, inositol triphosphate; PGE2, prostaglandin E2; PIP2, phosphatidylinositol 4,5-diphosphate; PKC, protein kinase C; PLC, protein lipase C; TGF-α, transforming growth factor α.
Digestion of lipids also starts in the stomach. The mixing patterns of gastric motility result in formation of an emulsion of lipids and gastric lipase, which attaches to the surface of lipid droplets in the emulsion and generates free fatty acids and monoglyceride from dietary triglyceride. However, the extent of hydrolysis of triglyceride is approximately 10%, and hydrolysis is not essential for normal digestion and absorption of dietary lipids. Moreover, as discussed in the next chapter, the products of lipolysis are not available for absorption in the stomach because of its low luminal pH.
Mucus and HCO3 − protect the surface of the stomach from the effects of H+ and pepsins. The protective mucus gel that forms on the luminal surface of the stomach, as well as alkaline secretions entrapped within it, constitute a gastric mucosal barrier that prevents damage to the mucosa by gastric contents (