title: Characterization of a decrease in muscarinic m2 mRNA in cerebellar granule cells by carbachol.
abstract: Studies involving carbachol (100 microM) treatment of cerebellar granule cells for 1, 3, 6, 9, 12 and 24 hr show a decrease in the mRNA encoding for the muscarinic m2 receptor. The response was transient, decreasing m2 mRNA by 25 to 50% in 6 and 9 hr, respectively. The data presented in this work were quantified by ribonuclease protection assay, using a [32P]-cRNA probe corresponding to nucleotide +1138 to 1650 of the rat m2 muscarinic receptor. Because cerebellar granule cells express muscarinic m2 and m3 receptors, we tested whether the carbachol-mediated decrease in m2 mRNA resulted from a homologous or heterologous activation of muscarinic receptors. At a 1 microM concentration, methoctramine specifically blocked the muscarinic m2 receptor and reversed carbachol's action. These data suggested that carbachol acts via a possible homologous activation of muscarinic m2 receptors. The half-life of the receptor mRNA measured in the presence of actinomycin D with and without carbachol were similar. Because carbachol treatments decrease the steady-state levels of m2 mRNA without changing the half-life of the message, we suggest that a carbachol treatment induces a decrease in the transcription of the gene for the muscarinic m2 receptor.
authors: Fidia Georgetown Institute for the Neurosciences, Georgetown University, School of Medicine, Washington, DC.
authors: P
authors: P
authors: Longone
authors: I
authors: I
authors: Mocchetti
authors: M A
authors: MA
authors: Riva
authors: W J
authors: WJ
authors: Wojcik
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D002217:Carbachol