Gastric acid secretion histamine

Soldani, G., Intorre, L., Bertini, S., Luchetti, E., Coruzzi, G., Bertaccini, G., 1994. Regulation of gastric acid secretion by histamine H3 receptors in the dogs an investigation into the site of action. Naunyn-Schmiedeberg s Arch. Pharmacol. 350, 218-223. 

Bertaccini G, Coruzzi G. Control of gastric acid secretion by histamine H2 receptor antagonists and anticholinergics. Pharmacol. Res., 1989, 21(4), 339-352. 

Figure 7-2. Determination of simultaneous absorption of (THO), Na, and from the stomach of a dog before and after stimulation of acid secretion with histamine. (From Code CF, Higgins JA, Moll JC, et al. Influence of acid on the gastric absorption of water, sodium and potassium. I Physiol Lond 166 110-119, 1963.)...

Histamine H2 Receptor Antagonists. In 1972 a new class of histamine antagonists was described that was capable of antagonizing histamine-induced gastric acid secretion (6). The H2 antagonists are divided into five stmctural classes, some of which are shown in Table 3. A more complete review can be found in Reference 25. 

Histamine is a biogenic amine that is widely distributed in the body and functions as a major mediator of inflammation and allergic reactions, as a physiological regulator of gastric acid secretion in the stomach, as a neurotransmitter in the central nervous system (CNS) and may also have a role in tissue growth and repair. 

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... 

Figure 3.1 A schematic representation of the control mechanism that stimulates gastric acid secretion, and the intervention points used to treat ulcers. The parietal cells and gastric cells form part of the epithelial cell lining of the stomach. Histamine release is usually triggered as part ofthe enteric nervous system response to distension of the stomach when food is eaten.

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

Gastrin is a hormone produced by gastric endocrine tissue — specifically, the G cells in the pyloric gland area. It is released into the blood and carried back to the stomach. The major function of gastrin is to enhance acid secretion by directly stimulating parietal cells (HC1) and chief cells (pepsinogen). Gastrin also stimulates the local release of histamine from enterochromaf-fin-like cells in the wall of the stomach. Histamine stimulates parietal cells to release HC1. 

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. 

In the intense search for inhibitors of gastric acid secretion a new class of potent histamine H2-receptor antagonist was discovered. These 1,2,5-thiadiazole-l-oxides (27) were prepared by nucleophilic addition of primary amines to 3,4-dialkoxy-l,2,5-thiadiazole 1-oxide (25). Sequential addition of two different amines to positions C(3) and C(4), respectively, could be achieved via the 3-alkoxy-4-amino adduct (26) (Scheme 5) <82JMC207,82JMC210>. 

In the mucosa of the gastrointestinal tract histamine is present in enterochromaffin cells. These cells are thought to contain the histamine which is involved in the stimulation of gastric acid secretion. In the central nervous system there are histaminergic neurons. 

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

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. 

A. Gastrin, histamine, and acetylchohne stimulate gastric acid secretion. Pepsin is a digestive protein secreted by the stomach in response to a meal. Norepinephrine is a neurotransmitter that does not affect gastric acid secretion. 

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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