PT - JOURNAL ARTICLE AU - Maudsley, Stuart AU - Martin, Bronwen AU - Gesty-Palmer, Diane AU - Cheung, Huey AU - Johnson, Calvin AU - Patel, Shamit AU - Becker, Kevin G. AU - Wood, William H. AU - Zhang, Yongqing AU - Lehrmann, Elin AU - Luttrell, Louis M. TI - Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo AID - 10.1124/mol.114.095224 DP - 2015 Jan 30 TA - Molecular Pharmacology PG - mol.114.095224 4099 - http://molpharm.aspetjournals.org/content/early/2015/01/30/mol.114.095224.short 4100 - http://molpharm.aspetjournals.org/content/early/2015/01/30/mol.114.095224.full AB - Biased G protein-coupled receptor agonists engender a restricted repertoire of downstream events from their cognate receptors, permitting them to produce mixed agonist-antagonist effects in vivo. While this opens the possibility of novel therapeutics, it complicates rational drug design, since the in vivo response to a biased agonist cannot be reliably predicted from its in vitro efficacy. We have employed novel informatic approaches to characterize the in vivo transcriptomic signature of the arrestin pathway-selective parathyroid hormone analog [D-Trp12, Tyr34]-bPTH(7-34) in six different murine tissues after chronic drug exposure. We find that [D-Trp12, Tyr34]-bPTH(7-34) elicits a distinctive arrestin-signaling focused transcriptomic response that is more coherently regulated across tissues than that of the pluripotent agonist, hPTH(1-34). This arrestin-focused network is closely associated with transcriptional control of cell growth and development. Our demonstration of a conserved arrestin-dependent transcriptomic signature suggests a framework within which the in vivo outcomes of arrestin-biased signaling may be generalized.