Gastric secretion, histamine effects

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... 

Cyproheptadine resembles the phenothiazine antihistaminic agents in chemical structure and has potent H receptor-blocking as well as 5-HT2-blocking actions. The actions of cyproheptadine are predictable from its histamine and 5-HT receptor affinities. It prevents the smooth muscle effects of both amines but has no effect on the gastric secretion stimulated by histamine. It also has significant antimuscarinic effects and causes sedation. 

The foregoing bases are usually employed as their salts with maleic, tartaric or hydrochloric acid. They usually depress the CNS, producing drowsiness and other side-effects that may preclude the use of a particular drug, but responses of different patients vary. Since antihistamine activity is shown by many compounds of varied structure it is suggested that they do not fit the histamine receptor completely as histamine does, but merely cover the anionic site, with their aryl residues adsorbed on some adjacent area. These compounds do not influence histamine-induced gastric secretion, and it was concluded that the latter effect is produced by a different type of histamine receptor, termed the H2 receptor. Most other effects of histamine are attributed to the Hi receptor. 

Bertaccini, G., Impicciatore, M., Mossini, F., 1971. Effects of some N-substituted histamine derivatives on gastric secretion. Naunyn-Schmiedeberg s Arch. Pharmacol. 269, 418. 

As a gastric secretagogue, alcohol stimulates the secretion of gastric juice, which is rich in acid and pepsin. Therefore, the consumption of alcohol is contraindicated in subjects with untreated acid-pepsin disease (Figure 68.2). In addition, alcohol releases histamine, which in turn releases gastric juice. This effect is not blocked by atropine. 

Uchida M, Ohba S, Ikarashi Y et al. (1993) Effect of the novel histamine H2 antagonist 5,6-dimethyl-2-[4-[3-(l-piperidinomethyl)phenoxy]-(z)-2-butenylamino]-4(lH)-pyrimidone dihydrochloride on histamine-induced gastric secretion in Heidenhain pouch dogs. Arzneim Forsch/Drug Res 43 873-876... 

Hj and Hj receptors Once released, histamine can exert local or widespread effects on smooth muscles and glands. It contracts many smooth muscles, such as those of the bronchi and gut, but markedly relaxes others, including those in small blood vessels. Histamine also is a potent stimulus of gastric acid secretion see above). Other, less prominent effects include formation of edema and stimulation of sensory nerve endings. Bronchoconstriction and contraction of the gut are mediated by Hj receptors. Gastric secretion results from the activation of Hj receptors and, accordingly, can be inhibited by Hj-receptor antagonists see Chapter 36). 

The administration of morphine is followed by a series of complex events. Analgesia, euphoria, addiction, and respiratory depression are stressed in the literature, but if morphine had only its effect on carbohydrate metabolism it would rank wdth insulin and phloridzin in interest if it had only its effect on smooth muscle it would rank with pilocarpine and physostigmine and if it had only its effect on gastric secretion and salivation it wmuld rank with histamine. But consideration of some effects is lost in the importance of analgesia and only possible counter indications to its use as an analgesic remain continuously on the experimental horizon. 

Both phentolamine and tolazoline are potent but rather nonspecific a-antagonists. Both drugs stimulate gastrointestinal smooth muscle, an action blocked by atropine, which would indicate cholinergic activity, and they both stimulate gastric secretion, possibly through release of histamine. Because of these and other side effects, the clinical applications of tolazoline and phentolamine also are limited to treating the symptoms of pheochromocytoma. 

I. Pharmacology. Cimetidine, ranitidine, famotidine, and nizatidine are selective competitive inhibitors of histamine on Hj receptors. These receptors modulate smooth muscle, vascular tone, and gastric secretions and may be involved in clinical effects associated with anaphylactic and anaphylactoid reactions, as well as ingestion of histamine or histamine-like substances (eg, scombroid fish poisoning). Cimetidine, as an inhibitor of cytochrome P-450 enzymes, has been proposed or studied in animals as an agent to block the production of toxic intermediate metabolites (eg, acetaminophen, carbon tetrachloride, halothane. 

Impromidine is a selective H2 agonist used as a diagnostic aid the potency varies between 9 and 100 times histamine depending on the test system [312, 314,315]. In humans, it produces maximal gastric acid secretion, an effect inhibited by cimetidine [316]. It is a potent inhibitor of histamine methyl transferase and diamine oxidase [315]. The two imidazole units and the... 

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