KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Pharmacy, School of
    • Pharmacy Scholarly Works
    • View Item
    •   KU ScholarWorks
    • Pharmacy, School of
    • Pharmacy Scholarly Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Activation of the JAK-STAT pathway by olanzapine is necessary for desensitization of serotonin2A receptor-stimulated phospholipase C signaling in rat frontal cortex but not serotonin2A receptor-stimulated hormone release

    Thumbnail
    View/Open
    Singh_2010.pdf (887.1Kb)
    Issue Date
    2010-07
    Author
    Singh, Rakesh K.
    Jia, Cuihong
    Garcia, Francesca
    Carrasco, Gonzalo A.
    Battaglia, George
    Muma, Nancy A.
    Publisher
    SAGE Publications
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
    Show full item record
    Abstract
    Chronic treatment with olanzapine causes desensitization of serotonin2A receptor signaling. The purpose of the current study is to further understand the mechanisms underlying this desensitization response of serotonin2A receptor signaling in vivo. We now report that desensitization of serotonin2A receptor stimulated-phospholipase C activity in rat frontal cortex induced by olanzapine is dependent on activation of the JAK-STAT pathway. Olanzapine treatment for 7 days significantly increased the levels of the regulator of G protein signaling (RGS7) protein, RGS7 mRNA levels, and activation of JAK2 in rat frontal cortex. Pretreatment with a JAK2 inhibitor AG490, significantly attenuated the olanzapine-induced reductions in serotonin2A receptor-stimulated phospholipase C activity and prevented the olanzapine-induced increases in RGS7 mRNA and protein levels. In contrast, inhibition of the JAK-STAT pathway with AG490 did not reverse the olanzapine-induced desensitization of the serotonin2A receptor pathway in the hypothalamic paraventricular nucleus mediating increases in plasma hormone levels. AG490 dose-dependently inhibited serotonin2A receptor-stimulated oxytocin and corticosterone release. Taken together, these results suggest that the olanzapine-induced increase in RGS7 expression is mediated by activation of JAK-STAT and is necessary for olanzapine-induced desensitization of serotonin2A receptor-stimulated phospholipase C activity in the frontal cortex but not serotonin2A receptor-stimulated hormone release.
    URI
    http://hdl.handle.net/1808/24394
    DOI
    https://doi.org/10.1177/0269881109103090
    Collections
    • Pharmacy Scholarly Works [280]
    Citation
    Singh, R. K., Jia, C., Garcia, F., Carrasco, G. A., Battaglia, G., & Muma, N. A. (2010). Activation of the JAK-STAT pathway by olanzapine is necessary for desensitization of serotonin2A receptor-stimulated phospholipase C signaling in rat frontal cortex but not serotonin2A receptor-stimulated hormone release. Journal of Psychopharmacology (Oxford, England), 24(7), 1079–1088. http://doi.org/10.1177/0269881109103090

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps