Neuropharmacology, 2006-09, Vol.51 (3), p.524-535
2006
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- Autor(en) / Beteiligte
- Titel
- Alterations in 5-HT2A receptor signaling in male and female transgenic rats over-expressing either Gq or RGS-insensitive Gq protein
- Ist Teil von
- Neuropharmacology, 2006-09, Vol.51 (3), p.524-535
- Ort / Verlag
- England
- Erscheinungsjahr
- 2006
- Quelle
- Elsevier ScienceDirect
- Beschreibungen/Notizen
- Serotonin 2A (5-HT2A) receptors are coupled to Galphaq and Galpha11 proteins to activate phospholipase C (PLC). Regulators of G-protein signaling proteins (RGS) modulate G-protein signaling by accelerating the intrinsic GTPase activity of Galphaq and Galpha11. This study investigated the effects of over-expression of wild-type Galphaq proteins (Gq-Tg) and over-expression of RGS-insensitive Galphaq proteins (G188S, RGSi-Tg) on 5-HT2A receptor mediated signaling in transgenic rats. Over-expression of wild-type Galphaq and RGS insensitive mutant Galphaq did not produce significant alterations in the levels of Galpha11, 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, GTPgammaS-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 Galphaq, 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-3908eISSN: 1873-7064DOI: 10.1016/j.neuropharm.2006.04.012Titel-ID: cdi_proquest_miscellaneous_68930144
- Format
- –
- Schlagworte
- Amphetamines - pharmacokinetics, Analysis of Variance, Animals, Animals, Genetically Modified, Blotting, Western - methods, Cerebral Cortex - drug effects, Cerebral Cortex - metabolism, Dose-Response Relationship, Drug, Female, GTP-Binding Protein alpha Subunits, Gq-G11 - genetics, GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism, Hormones - blood, In Situ Hybridization - methods, Isotopes - pharmacokinetics, Ketanserin - pharmacokinetics, Male, Mutant Proteins - metabolism, Protein Binding - drug effects, Radioimmunoassay - methods, Radioligand Assay - methods, Rats, Receptor, Serotonin, 5-HT2A - metabolism, RGS Proteins - genetics, RGS Proteins - metabolism, Serotonin Antagonists - pharmacokinetics, Serotonin Receptor Agonists - pharmacokinetics, Sex Characteristics, Signal Transduction - physiology, Type C Phospholipases - metabolism