Endothelin-1 increases the levels of mRNA and protein of muscarinic acetylcholine receptors and c-fosmRNA in cerebellar granule cells

Abstract
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 mRNA 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.

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