Alterations in 5-HT2A receptor signaling in male and female transgenic rats over-expressing either Gq or RGS-insensitive Gq protein

Ju Shi, Katerina J. Damjanoska, Bozena W. Zemaitaitis, Francisca Garcia, Gonzalo Carrasco, Nicole R. Sullivan, Yijin She, Kathleen H. Young, George Battaglia, Louis D. Van De Kar, David S. Howland, Nancy A. Muma

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11 Scopus citations

Abstract

Serotonin 2A (5-HT2A) receptors are coupled to Gαq and Gα11 proteins to activate phospholipase C (PLC). Regulators of G-protein signaling proteins (RGS) modulate G-protein signaling by accelerating the intrinsic GTPase activity of Gαq and Gα11. This study investigated the effects of over-expression of wild-type Gαq proteins (Gq-Tg) and over-expression of RGS-insensitive Gαq proteins (G188S, RGSi-Tg) on 5-HT2A receptor mediated signaling in transgenic rats. Over-expression of wild-type Gαq and RGS insensitive mutant Gαq did not produce significant alterations in the levels of Gα11, RGS2, RGS4, RGS7, RGS16 or 5-HT2A proteins. RGSi-Tg rats had higher oxytocin and corticosterone responses to (-)DOI, a 5-HT2A/2C receptor agonist, compared to Gq-Tg rats. RGSi-Tg and Gq-Tg rats had higher ACTH responses to (-)DOI compared to control rats. Similarly, 5-HT-stimulated PLC activity in the frontal cortex was higher in RGSi-Tg and Gq-Tg rats compared to control rats. In contrast, GTPγS-stimulated PLC activity was higher in Gq-Tg rats but not in RGSi-Tg rats compared to control rats. There was a small but statistically significant increase in the affinity of [125I]-DOI labeled 5-HT2A receptors in RGSi-Tg rats and Gq-Tg rats compared to controls. There were no significant differences in Bmax and Kd of [3H] ketanserin labeled 5-HT2A receptors among the three groups. These data suggest that the effect of RGS proteins on 5-HT2A receptor signaling is cell type specific. In transgenic rats over-expressing Gαq, endogenous RGS proteins have a negative effect on 5-HT2A receptor-mediated oxytocin release. In contrast, endogenous RGS protein had no impact on 5-HT2A receptor-mediated ACTH release in transgenic rats.

Original languageEnglish (US)
Pages (from-to)524-535
Number of pages12
JournalNeuropharmacology
Volume51
Issue number3
DOIs
StatePublished - Sep 1 2006

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Shi, J., Damjanoska, K. J., Zemaitaitis, B. W., Garcia, F., Carrasco, G., Sullivan, N. R., She, Y., Young, K. H., Battaglia, G., Van De Kar, L. D., Howland, D. S., & Muma, N. A. (2006). Alterations in 5-HT2A receptor signaling in male and female transgenic rats over-expressing either Gq or RGS-insensitive Gq protein. Neuropharmacology, 51(3), 524-535. https://doi.org/10.1016/j.neuropharm.2006.04.012