Muscarinic receptors mediating acid secretion in isolated rat gastric parietal cells are of M3 type

Please always quote using this URN: urn:nbn:de:bvb:20-opus-128337
  • Five subtypes of muscarinic receptors have been identified by pharmacological and molecular biological methods. The muscarinic receptor subtype mediating acid secretion at the level of the parietal cell was unknown. Therefore, this study was performed to characterize muscarinic receptors on rat gastric parietal cells using the 3 subtype-selective antagonists hexahydrosiladifenidol and silahexocyclium, which have high affinity for glandular M3 subtypes, and AF-DX 116, which has high affinity to cardiac M2 receptors. The affinity of theseFive subtypes of muscarinic receptors have been identified by pharmacological and molecular biological methods. The muscarinic receptor subtype mediating acid secretion at the level of the parietal cell was unknown. Therefore, this study was performed to characterize muscarinic receptors on rat gastric parietal cells using the 3 subtype-selective antagonists hexahydrosiladifenidol and silahexocyclium, which have high affinity for glandular M3 subtypes, and AF-DX 116, which has high affinity to cardiac M2 receptors. The affinity of these antagonists was determined by radioligand binding experiments. In addition, their inhibitory potency on carbachol-stimulated inositol phosphate production was investigated. Inhibition of carbachol-stimulated aminopyrine uptake was used as an indirect measure of proton production. Both M3 antagonists, hexahydrosiladifenidol and silahexocyclium, had nanomolar affinities for parietal cell muscarinic receptors and potently antagonized inositol phosphate production with nanomolar Ki values. Silahexocyclium similarly antagonized aminopyrine accumulation while hexahydrosiladifenidol behaved as a noncompetitive antagonist. AF-DX 116 was a low-affinity ligand and a weak competitive antagonist at parietal-cell muscarinic receptors. It was concluded that muscarinic M3 receptors mediate acid secretion probably by activation of the phosphoinositide second messenger system in rat gastric parietal cells.show moreshow less

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Metadaten
Author: A. Pfeiffer, H. Rochlitz, B. Noelke, R. Tacke, U. Moser, E. Mutschler, G. Lambrecht
URN:urn:nbn:de:bvb:20-opus-128337
Document Type:Journal article
Faculties:Fakultät für Chemie und Pharmazie / Institut für Anorganische Chemie
Language:English
Parent Title (English):Gastroenterology
Year of Completion:1990
Volume:98
Issue:1
Pagenumber:218-222
Source:Gastroenterology. 1990 Jan;98(1):218-22
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 546 Anorganische Chemie
Tag:animals; gastric acid/secretion; gastric/secretion parietal cells; hexahydrosiladifenidol; muscarinic receptors; muscarinic/drug effects receptors; muscarinic/physiology receptors; parasympatholytics; parasympatholytics/pharmacology; piperazines; piperazines/pharmacology; piperidines; piperidines/pharmacology; radioligand assay; rats; silahexocyclium
Release Date:2016/03/01
Licence (German):License LogoDeutsches Urheberrecht