Differences in agonist potency ratios at human m1 muscarinic receptors expressed in A9L and CHO cells.

A9L mouse fibroblast and Chinese hamster ovary (CHO) cells appear to differ in their complement of guanine-nucleotide binding proteins (G proteins) and/or isoform of effectors that lead to inositol-monophosphate formation. The influence of these cellular components on receptor activation was examined by comparing agonist-induced inositol monophosphate formation via human muscarinic m1 receptors expressed in the two cell lines. The rank order of agonist potencies of five full agonists differed in the two cell lines. In addition, differences in agonist potency ratios for two of the five agonists (carbachol and methacholine) suggest that the agonists differ in their activation of m1 receptors and this is reflected in differences in G protein coupling. The results provide biological evidence that muscarinic agonists differentially activate m1 receptors and that, at least for the systems examined in this study, receptor-effector coupling in a given system may depend on the structure of the agonist.