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 d iffer in their complement of guanine-nucleotide binding proteins (G pr oteins) and/or isoform of effecters that lead to inositol-monophosphat e formation. The influence of these cellular components on receptor ac tivation was examined by comparing agonist-induced inositol monophosph ate formation via human muscarinic mi receptors expressed in the two c ell lines. The rank order of agonist potencies of five full agonists d iffered in the two cell lines. In addition, differences in agonist pot ency ratios for two of the five agonists (carbachol and methacholine) suggest that the agonists differ in their activation of ml receptors a nd this is reflected in differences in G protein coupling The results provide biological evidence that muscarinic agonists differentially ac tivate mi receptors and that, at least for the systems examined in thi s study, receptor-effector coupling in a given system may depend on th e structure of the agonist.