Parietal cells receptors

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... 

Mast cells and enterochromaffin-like cells found in the interstitium and among parietal cells contain histamine, which acts on parietal cell receptors to stimulate the release of hydrochloric acid. The histamine receptor on parietal cells is designated as H2 and is blocked by H2 blockers such as cimetidine which are widely used to treat peptic ulcers. 

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-... 

A variety of agents has been reported to stimulate or inhibit acid secretion by a direct action on the parietal cell. Many of these (e.g., cAMP derivatives, forskolin) do not act through cellular receptors, whereas others are suggested to reflect the presence of parietal cell receptors. Although no direct evidence for a parietal cell location exists, the ability of some substances to inhibit histamine stimulation of acid secretion argues for the presence of a parietal cell receptor, because the action of histamine is direct. Even in these cases, caution is necessary to interpret the inhibition as being direct rather than due to the release of another inhibitor. With this caveat in mind, the parietal cell appears to contain inhibitory receptors for somatostatin, prostaglandins (PG, EP3), and EGF. Each of these has been shown to inhibit histamine stimulation of acid formation by isolated cell preparations. 

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... 

Vitamin B12 is special in as far as its absorption depends on the availability of several secretory proteins, the most important being the so-called intrinsic factor (IF). IF is produced by the parietal cells of the fundic mucosa in man and is secreted simultaneously with HC1. In the small intestine, vitamin B12 (extrinsic factor) binds to the alkali-stable gastric glycoprotein IF. The molecules form a complex that resists intestinal proteolysis. In the ileum, the IF-vitamin B 12-complex attaches to specific mucosal receptors of the microvilli as soon as the chymus reaches a neutral pH. Then either cobalamin alone or the complex as a whole enters the mucosal cell. 

Interaction of the food with the gastric mucosal layer is the normal trigger for gastric cells to release gastrin, which is then carried by the bloodstream to the parietal cells. Calcium ions and cyclic AMP act as intracellular messengers in the transfer of the signal from the receptors to the proton pumps of parietal cells where the acid is generated. 

The histamine2-receptor antagonists or H2RAs (cimetidine, famotidine, nizatidine, and ranitidine) and proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantopra-zole, and rabeprazole) reduce the amount of acid secreted into the stomach by gastric parietal cells. These agents are also helpful for nausea and vomiting related to gastric acid secretion. 

Gastric secretion. Stimulation of gastric acid production by vagal impulses involves an M-cholinoceptor subtype (M -receptor), probably associated with enterochromaffin cells. Pirenzepine (p. 106) displays a preferential affinity for this receptor subtype. Remarkably, the HCl-secreting parietal cells possess only Ma-receptors. Mi-receptors have also been demonstrated in the brain however, these cannot be reached by pirenzepine because its lipophilicity is too low to permit penetration of the blood-brain barrier. Pirenzepine was formerly used in the treatment of gastric and duodenal ulcers (p. 166). 

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. 

Ib. Inhibitors of add production. Acting on their respective receptors, the transmitter acetylcholine, the hormone gastrin, and histamine released intra-mucosally stimulate the parietal cells of the gastric mucosa to increase output of HCl. Histamine comes from entero-chromaffin-like (ECL) cells its release is stimulated by the vagus nerve (via Mi receptors) and hormonally by gastria The effects of acetylcholine and histamine can be abolished by orally applied antagonists that reach parietal cells via the blood. 

The cholinoceptor antagonist pi-renzepine, unlike atropine, prefers cho-linoceptors of the Mi type, does not penetrate into the OIS, and thus produces fewer atropine-like side effects (p. 104). The cholinoceptors on parietal cells probably belong to the M3 subtype. Hence, pirenzepine may act by blocking Ml receptors on ECL cells or submucosal neurons. 

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... 

Histamine also evokes a copious secretion of highly acidic gastric juice from the gastric glands at doses below those that influence blood pressure (32). This effect of histamine is mediated through 2 receptors on the parietal cells. The importance of this effect in scombroid poisoning is not knowi. Histamine also has some stimulant actions on salivary, pancreatic, intestinal, bronchial, and lacrimal secretions (32), but these effects are relatively unimportant. 

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. 

C. Histamine stimulates gastric acid secretion through an effect on Hj-receptors of gastric parietal cells. Although certain antihistamines are metabolized by cytochrome P450 enzymes, histamine does not induce their production. Histamine helps to maintain a wakeful state through an effect on Hj-receptors. Histamine-mediated hronchoconstriction is mediated by Hj-receptors, while histamine-mediated vasodilation occurs as a result of stimulation of Hi- and Hj-receptors. 

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. 

Famotidine (Pepcid) 4.3 (0.2) 3.5 (0.2) Antagonizes the receptors that control the secretion of HCl by the parietal cells. 

Mecftanism of Action AGI Hj-blocker and gastric acid secretion inhibitor that inhibits histamine action at histamine 2 receptors of parietal cells Therapeutic Effect Inhibits gastric acid secretion when fasting, at night, or when stimulated by food, caffeine, or insulin. 

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