Duodenal receptors

Duodenal receptors are also sensitive to the chemical composition of chyme and are able to detect the presence of lipids, excess hydrogen ion, and hyperosmotic chyme. These conditions also elicit the enterogastric reflex and release of the enterogastrones in order to decrease the rate of gastric emptying. 

Antacids are neutralizing agents. Examples are magnesium hydroxide, magnesium trisylicate and aluminium hydroxide. Prior to the introduction of histamine-H2 receptor antagonists and proton pump inhibitors, they were the standard drugs for the treatment of duodenal/ peptic ulcers. Today their clinical use is limited to the treatment of dyspepsia and the symptomatic relieve for patients with peptic ulcers. 

LiEL Y, SHANY s, SMIRNOFF p and SCHWARTZ B (1999) Estrogen increases 1,25-dihydroxyvitamin D receptors expression and bioresponse in the rat duodenal mucosa. Endocrinol 140, 280-85. 

As the volume of the chyme in the duodenum increases, it causes distension of the duodenal wall and stimulation of mechanoreceptors. This receptor stimulation elicits reflex inhibition of gastric motility mediated through the intrinsic and vagus nerves. Distension also causes release of gastric inhibitory peptide from the duodenum, which contributes to inhibition of gastric contractions. 

Once formed, 1,25-DHCC acts on duodenal epithelial cells as a lipid-soluble hormone. Its intracellular receptor (a Zn-finger protein) binds to response elements in enhancer regions of DNA to induce the synthesis of calcium-binding proteins thought to play a role in stimulating calcium uptake from the GI tract. 

The mechanism of iron and heme uptake by the intestine is becoming better understood 70-72), but clearly heme-iron is more efficiently absorbed from the gastrointestinal tract than inorganic iron 73-75), and there is a receptor for heme in the duodenal brush border membrane 76). Duodenal mucosal cells efficiently catabolize heme, and iron-transferrin can be detected in the plasma of blood vessels draining the intestinal segment shortly after Fe—heme—histidine is administered (75). 

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). 

This lack of complete effectiveness led to the hypothesis that a second type of histamine receptor existed. In 1972, Black et al. (55) discovered a new series of antagonists which they called H2 receptor blockers. Burimamide was the first highly effective H2 blocker, but it was poorly absorbed orally. The modified compound, metiamide, had better absorption but was found to cause granulocytopenia (57.58). Finally, cimetidine was tested and found to be a potent and relatively non-toxic antagonist (59). Cimetidine is now widely used clinically to treat duodenal ulcers, Zollinger-Ellison Syndrome and other gastric hypersecretory diseases (32). 

Nizatidine (Axid/ Axid AR [OTC]) [Gastric Antisecretory/ H2 Receptor Antagonist] Uses Duodenal ulcCTs, GERD, heartburn Action H2-Receptor antagonist D< Adults. Active ulcer 150 mg PO bid or 300 mg PO hs maint 150 mg PO hs GERD 150 mg PO bid Heartburn 75 mg PO bid... 

K. Takeuchi, H. Urawa, S. Kato, O. Fururkawa, H. Araki, Y. Sugimoto, A. Ichikawa, F. Ushikubi, S. Narumiya, Impaired duodenal bicarbonate secretion and mucosal integrity in mice lacking prostaglandin E-receptor subtype EP3, Gastroenterology 117 (1999) 1128. 

Bonner Tl, Buckley NJ, Young AC, et al Identification of a family of muscarinic ace-tylchohne receptor genes. Science 237 527-532, 1987 Booth M, Hunt JN, Miles JM, et al Comparison of gastric emptying and secretion in men and women with reference to prevalence of duodenal ulcer in each sex. Lancet 1 657-659, 1957... 

Coruzzi, C., Poli, E., Bertaccini, G., 1991b. Histamine receptors in isolated guinea pig duodenal muscle H3 receptors inhibit cholinergic neurotransmission. J. Pharmacol. Exp. Ther. 258, 325-331. 

Poli, E., C. Pozzoli, C., Coruzzi, G., Bertaccini, G., 1993. Histamine H3 receptor-mediated inhibition of duodenal cholinergic transmission is independent of intracellular cyclic AMP and GMP. Gen. Pharmacol. 24, 1273-1278. 

The cure rate for gastric and duodenal ulcers is comparable to the results with H2-receptor antagonists (44— 46). Relapses appear to be fewer with prostaglandin therapy (44,45). Healing of duodenal ulcers refractory to H2-receptor antagonists has been described. 

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