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.
Jackson
D A
DA
Department of Pharmacology, University of Washington, Seattle 98195-7750, USA.
Nathanson
N M
NM
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D012333:RNA, Messenger; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D016212:Transforming Growth Factor beta; D000242:Cyclic AMP