Down-regulation of phospholipase C-beta1 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(alphaq/11) and phospholipase C-beta1 (but not the beta3-or gamma1 isoforms) were observed. These results suggest that a selective down-regulation of phospholipase C-beta1 may play a role in adaptation to chronic muscarinic receptor activation.
Sorensen
S D
SD
Mental Health Research Institute and Department of Pharmacology, University of Michigan, Ann Arbor 48104-1687, USA.
Linseman
D A
DA
Fisher
S K
SK
D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000494:pharmacology; D054799:Phospholipase C beta; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D010095:Oxotremorine; C042743:oxotremorine M; D010738:Type C Phospholipases; C518033:PLCB1 protein, human; C518039:PLCB3 protein, human; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins