Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Modulation of mu opioid receptor desensitization in peripheral sensory neurons by phosphoinositide 3-kinase gamma.

Authors: C König, O Gavrilova-Ruch, G Segond von Banchet, R Bauer, M Grün, E Hirsch, I Rubio, S Schulz, S H Heinemann, H G Schaible, R Wetzker

Journal, date & volume: Neuroscience, 2010 Aug 11 , 169, 449-54

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20451587

Abstract
G protein-coupled opioid receptors undergo desensitization after prolonged agonist exposure. Recent in vitro studies of mu-opioid receptor (MOR) signaling revealed an involvement of phosphoinositide 3-kinases (PI3K) in agonist-induced MOR desensitization. Here we document a specific role of the G protein-coupled class IB isoform PI3Kgamma in MOR desensitization in mice and isolated sensory neurons. The tail-withdrawal nociception assay evidenced a compromised morphine-induced tolerance of PI3Kgamma-deficient mice compared to wild-type animals. Consistent with a role of PI3Kgamma in MOR signaling, PI3Kgamma was expressed in a subgroup of small-diameter dorsal root ganglia (DRG) along with MOR and the transient receptor potential vanilloid type 1 (TRPV1) receptor. In isolated DRG acute stimulation of MOR blocked voltage-gated calcium currents (VGCC) in both wild-type and PI3Kgamma-deficient DRG neurons. By contrast, following long-term opioid administration the attenuating effect of MOR was strongly compromised in wild-type DRG but not in PI3Kgamma-deficient DRG. Our results uncover PI3Kgamma as an essential modulator of long-term MOR desensitization and tolerance development induced by chronic opioid treatment in sensory neurons.