Inhibition by Nitric Oxide of the Uptake of [^3H]Serotonin into Rat Brain Synaptosomes

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Author(s)

Abstract

[<SUP>3</SUP>H]Serotonin (5-HT) uptake by synaptosomes of rat brain was dose-dependently inhibited by nitric oxide (NO) donors such as sodium nitroprusside (SNP), 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine, 3-morpholinosydnonimine and S-nitroso-L-cysteine (NO-CYS). The inhibitory effect was blocked by reduced hemoglobin. The effect was not mimicked by ferrocyanide and ferricyanide. 8-Bromoguanosine 3'', 5''-cyclic monophosphate (8-bromo cGMP) did not affect [<SUP>3</SUP>H]5-HT uptake into rat cortical synaptosomes. The reduced activity of [<SUP>3H</SUP>]5-HT uptake into the cortical synaptosomes pretreated with NO-CYS was partially reversed by washing the preparation after the treatment. Kinetic analysis showed that NO-CYS (100 μM) decreased the V<SUB>max</SUB> value without any change in the K<SUB>m</SUB> value. NO-CYS did not affect the specific binding of [<SUP>3</SUP>H]paroxetine, a ligand that binds to the 5-HT transporter, in membranes. NO-CYS and SNP, like iodoacetic acid and sodium cyanide, decreased the ATP content in cortical synaptosomes, but the effect on ATP content was not related to that on [<SUP>3</SUP>H]5-HT uptake. These findings suggest that NO inhibits reversibly [<SUP>3</SUP>H]5-HT uptake into rat brain synaptosomes without affecting the recognition site of the 5-HT transporter in a cGMP-independent manner, and the observed effect is not due to its metabolic effect.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 75(2), 123-128, 1997-10-01

    The Japanese Pharmacological Society

References:  28

Codes

  • NII Article ID (NAID)
    10008189516
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4326409
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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