TY - JOUR
T1 - Alterations in 5-HT2A receptor signaling in male and female transgenic rats over-expressing either Gq or RGS-insensitive Gq protein
AU - Shi, Ju
AU - Damjanoska, Katerina J.
AU - Zemaitaitis, Bozena W.
AU - Garcia, Francisca
AU - Carrasco, Gonzalo
AU - Sullivan, Nicole R.
AU - She, Yijin
AU - Young, Kathleen H.
AU - Battaglia, George
AU - Van De Kar, Louis D.
AU - Howland, David S.
AU - Muma, Nancy A.
PY - 2006/9
Y1 - 2006/9
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33747051984&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2006.04.012
DO - 10.1016/j.neuropharm.2006.04.012
M3 - Article
C2 - 16769091
AN - SCOPUS:33747051984
SN - 0028-3908
VL - 51
SP - 524
EP - 535
JO - Neuropharmacology
JF - Neuropharmacology
IS - 3
ER -