Tetrahydroaminoacridine increases m3-, but not m2-, muscarinic acetylcholine receptor mRNA levels in differentiating cerebellar granule cells

Abstract

We used Northern blot hybridization to determine whether 9-amino-1,2,3,4-tetrahydroacridine (THA), a potential antidementia drug, selectively altered the levels of muscarinic acetylcholine receptor (mAChR) mRNA in differentiating cerebellar granule cells. Granule cells were cultured for 8 days in media containing 15 mM K+, 25 mM K+ or 15 mM K+ plus 30 μM THA. High K+ markedly increased the levels of m2- and m3-mAChR mRNA in the surviving cells. In contrast, THA increased the levels of m3-mAChR mRNA, but had little or no effect on m2-mAChR mRNA levels. These results suggest that THA selectively up-regulates the synthesis of m3-mAChR mRNA.