Regulation of expression and function of m2 and m4 muscarinic receptors in cultured embryonic chick heart cells by transforming growth factor-beta 1.

Incubation of cultured embryonic chicken heart cells with transforming growth factor beta 1 (TGF-beta 1) resulted in a concentration- and time-dependent decrease in the number of muscarinic acetylcholine receptors (mAChR), which reached a maximum by 24 hr. Twenty-four hours following TGF-beta 1 treatment, cm2 and cm4 mAChR protein levels were decreased 59 and 41%, respectively, and cm2 mRNA and cm4 mRNA levels were both decreased by approximately 40%. Chick heart cells treated with TGF-beta 1 exhibited a decreased sensitivity for carbachol-mediated inhibition of adenylyl cyclase activity compared with control cells. Thus, TGF-beta 1 stimulation of chick heart cells results in decreases in the expression of both cm2 and cm4 mAChR and in muscarinic responsiveness.