[MI cholinergic receptors of gastric secretion: current status]

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)