Endothelin-1 increases the levels of mRNA and protein of muscarinic acetylcholine receptors and c-fos mRNA in cerebellar granule cells.
Endothelin-1 (ET-1) induced a time- and dose-dependent increase in the levels of mRNA of m2- and m3-muscarinic acetylcholine receptors (mAChRs) in cultured cerebellar granule cells. The levels of immunoprecipitable m3-mAChR protein and total mAChR binding sites were also increased by ET-1 treatment. The up-regulation of m2- and m3-mAChR was blocked by phorbol ester pretreatment to inhibit ET-1-stimulated phosphoinositide hydrolysis and was preceded by an increase in c-fos mRNA levels. Treatments that prevented ET-1-induced c-fos mRNA increase also abolished the subsequent m2- and m3-mAChR mRNA up-regulation, suggesting that c-Fos protein is involved in the ET-1-induced mAChR expression.
Section on Molecular Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
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Fukamauchi
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Chuang
D015075:2-Aminopurine / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002531:Cerebellum / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D016762:Genes, fos; D007163:Immunosorbent Techniques; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000235:genetics* / Q000378:metabolism
D016232:Endothelins; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D015240:Phorbol 12,13-Dibutyrate; D015075:2-Aminopurine; D003513:Cycloheximide