Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report about muscarinic M1 receptors involved in gastric secretion includes two preliminary summaries concerning: a) gastric secretion regulation and b) the evaluation of our knowledge on muscarinic receptors. Gastric secretion is related to secreting cell masses, chief cell and parietal cell masses, and involves some stimulant compounds such as acetylcholine, gastrin and histamine. The schemes of acid secretion stimulation are based on the interactions between these substances. Parietal cells would have specific receptors for each stimulant or histamine would be the final common mediator for all stimulants. Another scheme can be proposed in which gastrin activity would be related to an antagonism between inhibition effects of somatostatin and the suppression of this inhibition by an histamine-like mediator called antramine. The presence of two different receptors to acetylcholine has been demonstrated for long ago, nicotinic receptors (N) and muscarinic receptors (M.). Studies with agonist and antagonist compounds have allowed to distinguish M1 receptors in autonomic ganglia cells and M2 receptors in skeletal muscle. This difference between M and M receptors might be explained by the conformational structure of the receptors (fig. 1), which has also been used for understanding spatial conformation of the agonists and the antagonists (fig. 2, 3). Pharmacological evidence for distinct M1 and M2 muscarinic receptors was presented in 1978 by Goyal and Rattan; in addition receptor binding studies of atropine and acetylcholine have demonstrated that muscarinic antagonists do not distinguish receptor subtypes while agonists do it (fig. 4). Pirenzepin is a new gastric antisecretory tricyclic compound proposed for the treatment of peptic ulcer. It has a higher affinity for M1 receptors in some tissues (eg autonomic ganglia, cerebral cortex) than in other tissues (eg cardia muscle, smooth muscle from gastrointestinal tract). Low concentrations of pirenzepine displace radiolabeled ligands such as 3H QNB, in certain tissues with high affinity receptors, whereas much higher concentrations of pirenzepine are needed to displace these muscarinic antagonist in other tissues with low-affinity receptors (fig. 5). Pharmacological properties of pirenzepine are different from those of atropine (tab. I). Receptor binding studies have disclosed the ability of pirenzepine to discriminate between muscarinic receptors in different tissues. The lowest Ki, molar concentrations producing half-saturation of receptors, was found in autonomic ganglia, reflecting the great affinity of pirenzepine for the neural muscarinic receptor of this tissue (fig. 6).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[MI cholinergic receptors of gastric secretion: current status]. 286 50

N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)urea (L-634,366) was selected from a series of pyridylurea compounds with antisecretory activity as a potential therapeutic agent for the treatment of ulcer disease. L-634,366 was an effective inhibitor of gastric secretion evoked by gastrin, histamine and 2-desoxy-D-glucose (2-DG) in conscious dogs. Orally, L-634,366 was slightly less potent than the reference H2 receptor blocker, cimetidine as an inhibitor of secretion evoked by histamine, but was equipotent as an inhibitor of secretion evoked by gastrin and 2-DG. In vitro L-634,366 was a weak antagonist of histamine (H2) receptor responses in the guinea-pig atria and rat uterus; in the atria the antagonism appeared to be noncompetitive. In the anesthetized dog, L-634,366 possessed weak anticholinergic activity as compared to atropine in reducing vagally mediated cardiovascular, antral motor responses and with regard to antagonizing the pressor response to the muscarinic stimulant, McN 343-A. The anticholinergic activity of L-634,366 was lower and more selective than that of pirenzepine or atropine in producing mydriasis in mice, in antagonizing acetylcholine induced bradycardia in guinea-pig atria, methacholine and acetylcholine elicited contractions in the guinea-pig ileum and QNB binding to muscarinic receptors. L-634,366, like carbenoxolone, increased incorporation of 3H-glucosamine in gastric mucous indicating an increase in synthesis or turnover of mucous. L-634,366 is a novel compound possessing a broad spectrum of antisecretory activity; in vitro studies suggested a weak noncompetitive inhibition of the histamine-H2 receptor in atria.
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PMID:Gastric antisecretory and pharmacologic properties of N,N-dimethyl-N'-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)ur ea (L-634,366). 287 93