Down-regulation of phospholipase C-β1 following chronic muscarinic receptor activation

To determine whether prolonged activation of a phospholipase C-coupled receptor can lead to a down-regulation of its effector enzyme, SH-SY5Y neuroblastoma cells were incubated for 24 h with the muscarinic receptor agonist, oxotremorine-M. Under these conditions, significant reductions (46-53%) in muscarinic cholinergic receptor density, G(alpha q/11) and phospholipase C-beta(1) (but not the beta(3)-or gamma(1) isoforms) were observed. These results suggest that a selective down-regulation of phospholipase C-beta(1) may play a role in adaptation to chronic muscarinic receptor activation. (C) 1998 Elsevier Science B.V.