Prevention of muscarinic acetylcholine receptor down-regulation by chloroquine: antilysosomal or antimuscarinic mechanisms.

The effect of the antimalarial drug chloroquine on the carbachol-induced down-regulation of muscarinic acetylcholine receptors (mAChRs) was studied in the neuroblastoma-glioma hybrid NG108-15 cells. Chloroquine, which is proposed to have both antilysosomal and antimuscarinic effects (4,11), blocked the loss of both cell surface and total mAChRs as monitored by [3H]N-methyl-scopolamine (NMS) and [3H] quinuclidinyl benzilate (QNB) bindings respectively. To the contrary, NH4Cl, only an antilysosomal agent, had no effect on the loss of surface receptors, but blocked degradation of internalized receptors following the effect of carbachol. These findings demonstrate that chloroquine prevents the agonist-induced mAChR down-regulation in NG108-15 cells by both its antilysosomal and antimuscarinic effects.