Arrestin-mediated activation of p38 MAPK: molecular mechanisms and behavioral consequences

Handb Exp Pharmacol. 2014;219:281-92. doi: 10.1007/978-3-642-41199-1_14.


Studies of kappa opioid receptor signaling mechanisms during the last decade have demonstrated that agonist activation of the receptor results in Gβγ-dependent signaling and distinct arrestin-dependent signaling events. Gβγ-dependent signaling results in ion channel regulation causing neuronal inhibition, inhibition of transmitter release, and subsequent analgesic responses. In contrast, arrestin-dependent signaling events result in p38 MAPK activation and subsequent dysphoric and proaddictive behavioral responses. Resolution of these two branches of signaling cascades has enabled strategies designed to identify pathway-selective drugs that may have unique therapeutic utilities.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arrestins / metabolism*
  • Drug Design
  • GTP-Binding Protein beta Subunits / metabolism
  • GTP-Binding Protein gamma Subunits / metabolism
  • Humans
  • Receptors, Opioid, kappa / agonists
  • Receptors, Opioid, kappa / metabolism*
  • Signal Transduction / physiology
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Arrestins
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Receptors, Opioid, kappa
  • p38 Mitogen-Activated Protein Kinases