Is field (vagal) stimulation of gastric acid secretion mediated by M1 or non-M1 muscarinic receptors? A methodical problem exemplified in the mouse stomach in vitro.
1. Highly controversial claims have been put forward in the literature as to the involvement of either M1 or non-M1 muscarinic receptors in the field (vagal) stimulation of gastric acid secretion. This mini-review considers three available sets of data obtained in the mouse isolated, lumen-perfused stomach. 2. While pA2 values seemed to favour non-M1 receptors, a comparison between M1 selective versus non-selective antagonists on the one hand and field stimulation versus bethanechol stimulation on the other clearly pointed to M1 receptors being involved. 3. In the present review we discuss a novel experimental approach supporting the latter concept of M1 receptors. This novel approach provides a simple though provocative way to deal with the particular difficulties in determining pA2 values in the acid-secreting gastric mucosa. It is based on the rank order in the effects of different antagonists relative to their receptor type-dependent affinities, when employed at a fixed concentration, rather than on their pA2 values.
Kromer
W
W
Byk Gulden Pharmaceuticals, Department of Pharmacology, Konstanz, Germany.
Eltze
M
M
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D004025:Dicyclomine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D051379:Mice; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012044:Regression Analysis
D001626:Bethanechol Compounds; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D018723:Bethanechol; D010890:Pirenzepine; D004025:Dicyclomine; D001285:Atropine