INHIBITION OF PHOSPHOLIPASE-C BLOCKS OPIOID RECEPTOR-MEDIATED ACTIVATION OF GI PROTEINS

ACTIVATION of phospholipase C (PLC) in response to stimulation of delt a-opioid, m4 muscarinic and alpha 2 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 pro teins with no effect on opioid binding to the receptors. U73122 treatm ent also suppressed functional responses of m4 muscarinic and alpha 2 adrenergic receptors in NG108-15 cells. Furthermore, the G protein act ivation mediated by mu- and delta-opioid receptors and opioid receptor -like receptor (ORL1,) were abolished by U73122 in SK-N-SH neuroblasto ma cells. Inhibition of adenylyl cyclase induced by high concentration s of GTP was blocked by U73122, suggesting that blockade is at the lev el of G proteins. Our results thus indicated that inhibition of PLC le ads to blockade of Gi protein activation mediated by opioid receptors or other Gi-coupled receptors.