Gastrin antagonists

Castro et al.117) have recently been able to show with the aid of structure-activity studies that tripeptide and tetrapeptide derivatives such as Boc-(3-Ala-Trp-Met-Asp-NH2 51 a from the C-terminal region of gastrin without phenylalanine as a gastrin antagonist inhibit in vivo the gastrin-stimulated acid secretion. 

Production of Novel Derivatives of a Gastrin Antagonist (GWl) using Biotransformation... 

Production of novel derivatives of a gastrin antagonist (GW1) using biotransformation... 

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. 

Stimulation of gastric acid secretion is the most important response it is blocked only by Hj antagonists. As mentioned before, the hormone gastrin may be involved in histamine release, because Hj antagonists block gastrin-induced acid secretion. 

Actions The histamine H2-receptor antagonists—cimetidine, ranitidine, famotidine, and nizatidine—act on H2-receptors in the stomach, blood vessels, and other sites. They are competitive antagonists of histamine and are fully reversible. These agents completely inhibit gastric acid secretion induced by histamine, or gastrin. However, they only partially inhibit gastric acid secretion induced by acetylcholine or bethanechol. 

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