Parietal cells H2-receptors

The H2 antagonists exhibit competitive inhibition at the parietal cell H2 receptor and suppress basal and meal-stimulated acid secretion (Figure 62-2) in a linear, dose-dependent manner. They are highly selective and do not affect H j or H3 receptors (see Chapter 16). The volume of gastric secretion and the concentration of pepsin are also reduced. 

Histamine receptors on parietal cells belong to the H2 type (p. 114) and are blocked by H2-antihistaniines. Because histamine plays a pivotal role in the activation of parietal cells, H2-anti-histamines also diminish responsivity to other stimulants, e.g gastrin (in gas-2000 Thieme... 

The parietal cell contains receptors for gastrin (CCK-B), histamine (H2), and acetylcholine (muscarinic, M3) (Figure 62-1). When acetylcholine (from vagal postganglionic nerves) or gastrin (released from antral G cells into the blood) bind to the parietal cell receptors, they cause an increase in cytosolic calcium, which in turn stimulates... 

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). 

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... 

Histamine (B). Histamine is stored in basophils and tissue mast cells. It plays a role in inflammatory and allergic reactions (p. 72, 326) and produces bronchoconstriction, increased intestinal peristalsis, and dilation and increased permeability of small blood vessels. In the gastric mucosa, it is released from enterochromaffin-like cells and stimulates acid secretion by the parietal cells. In the CNS, it acts as a neuromodulator. Two receptor subtypes (G-pro-tein-coupled), H and H2. are of therapeutic importance both mediate vascular responses. Prejunctional H3 receptors exist in brain and the periphery. 

H2-receptor antagonists are drugs used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. These drugs are used in the treatment of dyspepsia however, their use has waned since the advent of the more effective proton pump inhibitors. 

D. Ranitidine is an H2-receptor antagonist. H2-receptors are found in the cell membrane of parietal cells, not in the nucleus, nucleolus, or cytoplasm. Mammalian cells do not have cell walls. 

Histamine has long been recognized as a powerful stimulant of gastric acid secretion and, to a lesser extent, of gastric pepsin and intrinsic factor production. The effect is caused by activation of H2 receptors on gastric parietal cells and is associated with increased adenylyl... 

In close proximity to the parietal cells are gut endocrine cells called enterochromaffin-like (ECL) cells. ECL cells also have receptors for gastrin and acetylcholine, which stimulate histamine release. Histamine binds to the H2 receptor on the parietal cell, resulting in activation of adenylyl cyclase, which increases intracellular cyclic adenosine... 

Figure 3. Effect of N -methylhistamine produced by Helicobacter pylori on acid secretion On the one hand, this compound may reduce acid secretion by inhibiting, via H3 receptor activation, histamine synthesis and release from ECL cells on the other hand, FI3 receptor activation on D cells, with consequent inhibition of somatostatin release, may increase acid secretion. Additionally, direct activation of H2 receptors on parietal cell by N -metylhistamine must also be considered (this mechanism is not shown in the scheme).

The proton pump (H+K+ATPase) of the apical membrane of the parietal cells is the ultimate mechanism that governs acid secretion. Among a family of benzimidazole derivatives, omeprazole (Losec) promotes the healing of ulcers in the stomach, duodenum, and esophagus, and is of special value in patients who do not respond to H2-receptor antagonists. 

Schematic diagram of one model of the physiologic control of hydrogen ion secretion by the gastric parietal cell. ECL cell, enterochromaffin-like cell G(CCK-B), gastrin-cholecystokinin-B receptor H, histamine H2, histamine H2 receptor Mi, M3, muscarinic receptors ST2, somatostatin2 receptor ATPase, K /H ATPase proton pump. Some investigators place histamine receptors—and possibly cholinoceptors—on nearby tissue cells rather than on the parietal cell itself. (Modified and redrawn from Sachs G, Prinz C Gastric enterochromaffin-like cells and the regulation of acid secretion. News Physiol Sci 1996 11 57, and other sources.)...

Proton pump inhibitors, like H2-receptor antagonists, act at parietal cells and decrease gastric acid secretion. Proton pump inhibitors specifically block proton pumps,... 

Omeprazole itself is not the active inhibitor of the H+, K+-ATPase, however. Rather, the transformation of omeprazole in acid is required to inhibit the H+, K+-ATPase in vitro and in vivo, whereas intact omeprazole is devoid of inhibitory action. Isolated H+, K+-ATPase is blocked by omeprazole only after the pretreatment of omeprazole with acid. Conversely, neutralization of the acid-secretory canaliculi of isolated gastric gland and parietal cell preparations by permeable buffers, which blocks the acid-catalyzed transformation of omeprazole, prevents inhibition of the enzyme. Furthermore, in-vivo blockade of acid secretion using an H2-receptor antagonist prior to omeprazole administration decreases the inhibitory potency of omeprazole, whereas the stimulation of acid secretion (e.g., by food intake) increases the potency. 

The limited distribution of the H+, K+-ATPase, which is found mainly in the tubulovesicular and canalicular membranes of the gastric parietal cell. This is in contrast to, for example, the more widely distributed H2 and cholinergic receptors. 

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