Desensitization of the mu-opioid activation of phospholipase C in SH-SY5Y cells: the role of protein kinases C and A and Ca(2+)-activated K+ currents

British Journal of Pharmacology
D Smart, D G Lambert

Abstract

1. In SH-SY5Y cells, mu-opioids cause a rapidly desensitizing activation of phospholipase C (PLC), that appears secondary to Ca2+ influx via L-type voltage-sensitive Ca2+ channels (VSCCs). The aim of the present study was to characterize the mechanisms of desensitization of the mu-opioid-induced inositol (1,4,5) triphosphate (Ins(1,4,5)P3) response, by use of a stereospecific radioreceptor mass assay. 2. (R+)-Bay K 8644 (1 nM-10 microM) dose-dependently inhibited fentanyl-induced Ins(1,4,5)P3 formation, with an IC50 of 28.5 nM, confirming our earlier observations that mu-opioids open L-type VSCCs, thus allowing Ca2+ influx to activate PLC. 3. Ro 31-8220 (0.1 nM-10 microM), a protein kinase C inhibitor, dose-dependently enhanced fentanyl-induced Ins(1,4,5)P3 formation (EC50 = 20.0 nM), whilst acute phorbol 12,13-dibutrate (1 microM) abolished the response. 4. H-89 (1 nM-10 microM), a protein kinase A inhibitor, also dose-dependently enhanced fentanyl-induced Ins(1,4,5)P3 formation (EC50 = 93 nM), whilst dibutryl cyclic AMP (0.5 mM) abolished the response. 5. Blockade of Ca(2+)-activated K+ currents with 4-aminopyridine (2 mM) or iberiotoxin (10 nM) had no effect on fentanyl-induced Ins(1,4,5)P3 formation but further increased th...Continue Reading

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Citations

Sep 29, 2011·Cellular and Molecular Neurobiology·Jia-Ming BianJin Li
Jun 3, 1996·European Journal of Pharmacology·D Smart, D G Lambert
Aug 18, 2000·Anaesthesia·I M Aguilera, R S Vaughan
Jul 30, 1997·Biochemical and Biophysical Research Communications·L G Lou, G Pei
Jan 30, 2002·Brain Research·Sandra M SiegelPatrick A Carr
Dec 6, 1997·Biochemical and Biophysical Research Communications·L G LouG Pei
Nov 27, 1999·Annales Françaises D'anesthèsie Et De Rèanimation·A MullerJ P Loeffler
Jun 6, 2006·Cellular Signalling·Nicolas MarieStéphane Allouche

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