Inhibition of phospholipase C blocks opioid receptor-mediated activation of Gi proteins.
Activation of phospholipase C (PLC) in response to stimulation of delta-opioid, m4 muscarinic and alpha2 adrenergic receptors was observed in NG108-15 cells. Treatment with PLC specific inhibitors, U73122 and ET-18-OCH3, blocked delta-opioid receptor-mediated activation of G proteins with no effect on opioid binding to the receptors. U73122 treatment also suppressed functional responses of m4 muscarinic and alpha2 adrenergic receptors in NG108-15 cells. Furthermore, the G protein activation mediated by mu- and delta-opioid receptors and opioid receptor-like receptor (ORL1) were abolished by U73122 in SK-N-SH neuroblastoma cells. Inhibition of adenylyl cyclase induced by high concentrations of GTP was blocked by U73122, suggesting that blockade is at the level of G proteins. Our results thus indicated that inhibition of PLC leads to blockade of Gi protein activation mediated by opioid receptors or other Gi-coupled receptors.
Wu
Y L
YL
Shanghai Institute of Cell Biology, Chinese Academy of Sciences, People's Republic of China.
Pei
G
G
Fan
G H
GH
D002460:Cell Line; D004963:Estrenes / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000187:drug effects*; D016015:Logistic Models; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D010742:Phospholipid Ethers; D011760:Pyrrolidinones; D011957:Receptors, Opioid; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C026659:edelfosine; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins