1. Pharmacological properties of cloned muscarinic receptors expressed in A9 L cells; comparison with in vitro models
- Subjects
molecular cloning ,3' quinuclidine] ,8 dimethyl 1 ,muscarine ,4' [1 ,animal cell ,8 diazaspiro[4.5]decane 1 ,methylfurtrethonium ,muscarinic M3 receptor ,3 dioxolane 4 ,atropine methyl nitrate ,telenzepine ,muscarinic M1receptors ,n methyl n (1 methyl 4 pyrrolidino 2 butynyl)acetamide ,3 dione ,methoctramine ,rat ,superior cervical ganglion ,calcium cell level ,pirenzepine ,muscarinic M3receptors ,article ,cell line ,2' dimethylspiro[piperidine 4 ,carbachol ,unclassified drug ,2 ethyl 8 methyl 2 ,para fluorohexahydrosiladifenidol ,muscarinic M1 receptor ,priority journal ,ileum ,[4 [(3 chlorophenyl)carbamoyloxy] 2 butynyl]trimethylammonium ,3]dioxolane] ,otenzepad ,oxotremorine ,animal tissue ,male ,3 dioxa 8 azaspiro[4.5]decane ,controlled study ,mouse ,4 diphenylacetoxy 1 methylpiperidine ,A9L cells (mouse fibroblast) ,nonhuman ,muscarinic agent ,arecoline ,pilocarpine ,2 methylspiro[1 ,concentration response ,cevimeline ,gene expression ,muscarinic receptors (cloned) ,muscarinic receptor blocking agent ,guinea pig - Abstract
The effects of a series of muscarinic agonists and antagonists at cloned m1 and m3 muscarinic receptors expressed in mouse fibroblast A9 L cells have been compared with their effects in in vitro models of M1(rat superior cervical ganglion) and M3(guinea-pig ileum) muscarinic receptors. A good correlation existed between the potencies of muscarinic agonists at cloned ml muscarinic receptors and the M1sites in rat ganglion (r = 0.80) as well as at cloned m3 receptors and guinea-pig ileum M3receptors (r = 0.87). However, cross correlations of potencies in rat ganglion and cloned m3 receptors as well as in guinea-pig ileum and in cloned m3 receptors also yielded relatively high correlation coefficients (0.71 and 0.91, respectively). Low correlation coefficients were found for the maximal responses of muscarinic agonists in rat ganglion and cloned m1 receptors (0.53) and in guinea-pig ileum and cloned m3 receptors (0.36). A high correlation between pA2values of muscarinic antagonists at cloned m1 receptors and in rat ganglion (r = 0.97) and between cloned m3 receptors and guinea-pig ileum (r = 0.98) was found. Cross correlation of pA2values in rat ganglion and cloned m3 receptors and in guinea-pig ileum and cloned m1 receptors yielded correlation coefficients of 0.82 and 0.72, respectively. The data indicate that the cloned muscarinic receptor sites seem similar to the corresponding endogenous sites. The good correlations in corresponding but also non-corresponding receptor models reflect the relatively low selectivity of the majority of the compounds investigated.
- Published
- 1991