1990 Fiscal Year Final Research Report Summary
Hyperresponsiveness of 5-HT-2 Receptor-Mediated Intracellular Camobilization in Platelets from the Depressed Patients and in C6 Glioma Cells Pretreated with Dexamethasone.
| Project/Area Number |
01570621
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Div. of Mental Disorder Res., Natl. Institute of Neurosci., NCNP |
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Principal Investigator |
MIKUNI Masahiko 国立精神・神経センター, 神経研究所, 室長 (00125353)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Toru Natl. Institute of Neurosci. Chief, 神経センター神経研究所, 室長 (00198441)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Serotonin-2 receptor / Phosphatidylinositol / Ca mobilization / Platelet / C6 glioma calls / Affective disorders / GTP binding protein / Hypothalamo-Pituitary-Adrenocortical Axis |
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| Research Abstract |
The increase in intracellular Ca ion concentration induced by 10uM 5-HT in platelets from 11 normal controls was 109+/-6nM, while that from 11 depressed patients was 131+/-5nM, which was significantly higher than that of normal controls. These results are consistent with our previous observation that 5-HT-stimulated inositol phospholipid hydrolysis in platelets from depressed patient is greater than that of normal controls, suggesting that 5-HT-2 receptor function in platelets is enhanced in patients with affective disorders. To clarify what kind of mechanism produces the enhanced 5-HT-2 receptor function in the central nervous system, we also investigated the effect of dexamethasone or ACTH treatment on 5-HT-induced Ca ion mobilization in C6 glioma cells and on the density of 5-HT-2 receptors in rat cerebral cortex. 48-hour treatment with 100nM dexamethasone enhanced 5-HT-2 receptor-mediated Ca ion mobilization in C6 glioma cells and 10-day treatment with ACTH (50ug/day) produced an increase in the density of 5-HT-2 receptors in rat cerebral cortex, suggesting that the disinhibition of Hypothalamo-Pituitary-Adreno-cortical axis may be, in part, responsible for enhancing 5-HT-2 receptor function in the affective disorders. In this preliminary study, we also demonstrated that several antidepressant agents reduced the affinity and increased the rate of H3-GTP binding to crude membranes from rat cerebral cortex as well as these agents enhanced the GTPase activity of reconstituted Co, suggesting that these antidepressants are capable of interacting with G proteins in brain membranes to cause the direct activation.
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