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  • 1
    ISSN: 1435-1463
    Keywords: Serotonin2 receptor ; α2-adrenergic receptor ; calcium mobilization ; heterologous supersensitization ; human platelets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent reports suggest that serotonin (5-HT)2 receptor-mediated second messenger systems are enhanced in platelets of affective disorders. To make the mechanism of the enhanced response clear, we investigated 5-HT2 and alpha (α)2-adrenergic receptor-induced intracellular calcium (Ca2+) mobilization in platelets of healthy volunteers, using fura-2. 5-HT2 and α2-adrenergic receptor-mediated Ca2+ mobilization was enhanced by prior exposure to the other type of agonist, so called “heterologous supersensitization”. The supersensitization was due to the enhancement of maximal response without change in agonist affinity. Chelating extracellular Ca2+ did not diminish the supersensitization. This enhancement of Ca2+ mobilization was not inhibited by H-7, an inhibitor of protein kinase C. However, this supersensitization was inhibited by pretreatment with sodium fluoride which directly activates guanine nucleotide binding regulatory proteins (G proteins). These results suggest that the supersensitization was caused from intracellular Ca2+ storage sites through a G protein-coupled pathway.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: 5-HT-2 receptors ; cGMP generation ; nitric oxide ; desensitization ; C6 glioma cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serotonin (5-HT)-2 receptor-mediated cGMP generation was investigated in comparison with calcium (Ca2+) mobilization in C6 glioma cells. 5-HT enhanced cGMP generation, and risperidone and ketanserin potently blocked the response. These results indicate that 5-HT-2 receptors are responsible for the cGMP generation. 5-HT-induced cGMP production was completely abolished by BAPTA, an intracellular Ca2+ chelating agent, or N g -monomethyl-L-arginine (NMMA), a nitric oxide synthase (NOS) inhibitor, suggesting that 5-HT-induced cGMP generation was through nitric oxide (NO)-dependent pathway. 5-HT (10 μM)-elicited Ca2+ mobilization and cGMP generation were reduced to 40 and 15 % after pretreatment with 10 μM 5-HT for 4 hours. NMMA did not modify 5-HT-induced desensitization of either Ca2+ mobilization or cGMP generation, suggesting that NO pathway is independent of the desensitization. The present study has demonstrated the nature of 5-HT-2 receptormediated cGMP generation in C6 glioma cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: Keywords: Heat shock protein ; calcium ; serotonin ; 5-HT-2A receptors ; quercetin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. This study was conducted to investigate an effect of heat stress at 44°C for 30 min on intracellular Ca2+ signaling system and on heat shock protein (HSP)-70 expression. 5-HT-induced Ca2+ mobilization was reduced 1, 3 and 6 hrs after heat stress, and recovered to the control level 12 and 24 hrs after heat stress. One hr after heat stress, Ca2+ rise was significantly decreased when the cells were stimulated by any concentration of 5-HT. Thrombin-induced Ca2+ increase was also markedly reduced 1 hr after heat stress. HSP-70 level was increased 6 and 9 hr after heat stress. In HSP synthesis inhibitor quercetin-treated cells, HSP-70 expression was not enhanced after heat stress, and Ca2+ rise in response to 5-HT did not return to the control level. However, the Ca2+ rise induced by 5-HT was not restored to the control level after stress in Ac-Asp-Glu-Val-Asp-H (DEVD)-exposed cells while DEVD had little effect on heat stress-induced synthesis of HSP-70. Dexamethasone did not alter the change in HSP-70 expression or Ca2+ response after heat stress. These results indicate that heat stress attenuated 5-HT-induced Ca2+ mobilization and that HSP-70 expression played an important role in recovery from Ca2+ impairment, possibly via protease activity in C6 cells.
    Type of Medium: Electronic Resource
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