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    Evidence that GZ proteins couple to hypothalamic 5-HT1A receptors in vivo

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    MumaN_JN_20(9)3095.pdf (236.7Kb)
    Issue Date
    2000-05-01
    Author
    Serres, F.
    Li, Qian
    Garcia, Francisca
    Raap, Danı́ K.
    Battaglia, George
    Muma, Nancy A.
    Van de Kar, Louis D.
    Publisher
    Society for Neuroscience
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Published Version
    http://www.jneurosci.org/content/20/9/3095.short
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    Abstract
    Using in situ hybridization and immunoblot analysis, the present studies identified Gz mRNA and Gz-protein in the hypothalamic paraventricular nucleus. The role of Gz-proteins in hypothalamic 5-HT1Areceptor signaling was examined in vivo. Activation of 5-HT1A receptors increases the secretion of oxytocin and ACTH, but not prolactin. Intracerebroventricular infusion (3–4 d) of Gz antisense oligodeoxynucleotides, with different sequences and different phosphorothioate modification patterns, reduced the levels of Gz-protein in the hypothalamic paraventricular nucleus, whereas missense oligodeoxynucleotides had no effect. Neither antisense nor missense oligodeoxynucleotide treatment altered basal plasma levels of ACTH, oxytocin, or prolactin, when compared with untreated controls. An antisense-induced decrease in hypothalamic Gz-protein levels was paralleled by a significant decrease in the oxytocin and ACTH responses to the 5-HT1A agonist 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT). In contrast, the prolactin response to 8-OH-DPAT (which cannot be blocked by 5-HT1A antagonists) was not inhibited by Gz antisense oligodeoxynucleotides. Gz-proteins are the only members of the Gi/Go-protein family that are not inactivated by pertussis toxin. In a control experiment, pertussis toxin treatment (1μg/5 μl, i.c.v.; 48 hr before the 8-OH-DPAT challenge) did not inhibit the ACTH response, potentiated the oxytocin response, and eliminated the prolactin response to 8-OH-DPAT. Thus, pertussis toxin-sensitive Gi/Go-proteins do not mediate the 5-HT1A receptor-mediated increase in ACTH and oxytocin secretion. Combined, these studies provide the firstin vivo evidence for a key role of Gz-proteins in coupling hypothalamic 5-HT1Areceptors to effector mechanisms.
    Description
    This is the publisher's version, also available electronically from "http://www.jneurosci.org".
    URI
    http://hdl.handle.net/1808/17701
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    • Pharmacy Scholarly Works [280]
    Citation
    Serres, F., Li, Q., Garcia, F., Raap, D.K., et al. (2000) Evidence that GZ proteins couple to hypothalamic 5-HT1A receptors in vivo. The Journal of Neuroscience, 20(9), 3095-3103.

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    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
     

     

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