Table of Contents
Journal of Signal Transduction
Volume 2012, Article ID 210324, 6 pages
http://dx.doi.org/10.1155/2012/210324
Research Article

Dopamine D 2 Receptor-Mediated Heterologous Sensitization of AC5 Requires Signalosome Assembly

1Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907-2051, USA
2Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
3Department of Pharmacology Therapeutics, McGill University, McIntyre Medical Sciences Building, Montréal, QC, Canada H3G 1Y6

Received 7 October 2011; Accepted 28 December 2011

Academic Editor: J. Adolfo García-Sáinz

Copyright © 2012 Karin F. K. Ejendal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chronic dopamine receptor activation is implicated in several central nervous system disorders. Although acute activation of G 𝛼 i -coupled D2 dopamine receptors inhibits adenylyl cyclase, persistent activation enhances adenylyl cyclase activity, a phenomenon called heterologous sensitization. Previous work revealed a requirement for G 𝛼 s in D2-induced heterologous sensitization of AC5. To elucidate the mechanism of G 𝛼 s dependency, we expressed G 𝛼 s mutants in G 𝛼 s -deficient 𝐺 𝑛 𝑎 𝑠 E 2 / E 2 cells. Neither G 𝛼 s -palmitoylation nor G 𝛼 s -Gβγ interactions were required for sensitization of AC5. Moreover, we found that coexpressing βARKct-CD8 or Sar1(H79G) blocked heterologous sensitization. These studies are consistent with a role for G 𝛼 s -AC5 interactions in sensitization however, Gβγ appears to have an indirect role in heterologous sensitization of AC5, possibly by promoting proper signalosome assembly.