Alterations in 5-HT2A receptor signaling in male and female transgenic rats over-expressing either Gq or RGS-insensitive Gq protein
| Autor: | Nicole R. Sullivan, Louis D. Van de Kar, Yijin She, Bozena Zemaitaitis, Kathleen H. Young, Nancy A. Muma, Gonzalo A. Carrasco, Francisca Garcia, Katerina J. Damjanoska, David Howland, George Battaglia, Ju Shi |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Agonist medicine.medical_specialty Ketanserin medicine.drug_class Blotting Western Radioimmunoassay Animals Genetically Modified Radioligand Assay Cellular and Molecular Neuroscience Isotopes Internal medicine medicine Animals Receptor Serotonin 5-HT2A Receptor In Situ Hybridization RGS2 5-HT receptor Cerebral Cortex Pharmacology Analysis of Variance Sex Characteristics Dose-Response Relationship Drug biology Phospholipase C Amphetamines Hormones Rats Serotonin Receptor Agonists Endocrinology Gq alpha subunit Type C Phospholipases biology.protein GTP-Binding Protein alpha Subunits Gq-G11 Female Mutant Proteins Serotonin Antagonists RGS Proteins hormones hormone substitutes and hormone antagonists Protein Binding Signal Transduction medicine.drug |
| Zdroj: | Neuropharmacology. 51:524-535 |
| ISSN: | 0028-3908 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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