title: Arrestin-mediated activation of p38 MAPK: molecular mechanisms and behavioral consequences.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA, 98195, USA, cchavkin@u.washington.edu.
authors.forename: Charles
authors.initials: C
authors.lastname: Chavkin
authors.forename: Selena S
authors.initials: SS
authors.lastname: Schattauer
authors.forename: Jamie R
authors.initials: JR
authors.lastname: Levin
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D015195:Drug Design; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D006801:Humans; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D019390:Arrestins; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D017473:Receptors, Opioid, kappa; D048051:p38 Mitogen-Activated Protein Kinases