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Heterologous supersensitization between serotonin2 and alpha2-adrenergic receptor-mediated intracellular calcium mobilization in human platelets

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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.

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Abbreviations

fura-2/AM :

1-(2-(5“-carboxyoxazol-2”-yl)-6-aminobenzofuran-5-oxy)-2-(2′-amino-5′-methylphenoxy)-ethane-N,N,N′, N′-tetraacetic acid, pentaacetoxymethyl ester

H-7 :

1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride

EGTA :

ethylenedioxybis(ethylamine)-N,N,N′,N′-tetraacetic acid

HEPES :

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

NaF :

sodium fluoride

Fmax :

maximal fluorescence intensity

Fmin :

minimal fluorescence intensity

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Author notes

  1. M. Mikuni

    Present address: Division of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo

  2. H. Yamamoto

    Present address: Department of Psychopharmacology, Psychiatric Research Institute of Tokyo, Tokyo, Japan

Authors and Affiliations

  1. Division of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo

    A. Kagaya, H. Yamamoto, S. Muraoka & K. Takahashi

  2. Department of Neurology and Psychiatry, Hiroshima University School of Medicine, Hiroshima, Japan

    A. Kagaya & S. Yamawaki

Authors
  1. A. Kagaya
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  2. M. Mikuni
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  3. H. Yamamoto
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  4. S. Muraoka
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  5. S. Yamawaki
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  6. K. Takahashi
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Kagaya, A., Mikuni, M., Yamamoto, H. et al. Heterologous supersensitization between serotonin2 and alpha2-adrenergic receptor-mediated intracellular calcium mobilization in human platelets. J. Neural Transmission 88, 25–36 (1992). https://doi.org/10.1007/BF01245034

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  • DOI: https://doi.org/10.1007/BF01245034

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