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Nitric oxide inhibits [3H]dopamine uptake

S Pogun1, M H Baumann, M J Kuhar

  • 1Neuroscience Branch, National Institutes of Health, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.

Brain Research
|March 28, 1994
PubMed
Summary

Nitric oxide (NO), generated by sodium nitroprusside, reduces dopamine uptake in brain cells. This effect is specific to dopamine transporters and not caused by direct drug binding.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Nitric oxide (NO) is a signaling molecule implicated in various physiological processes.
  • The precise mechanisms by which NO influences neurotransmitter transporter function remain incompletely understood.

Purpose of the Study:

  • To investigate the effect of nitric oxide (NO) on dopamine transporter (DAT) function.
  • To elucidate the role of NO in regulating [3H]dopamine uptake.

Main Methods:

  • Utilized rat striatal synaptosomal preparations to measure [3H]dopamine uptake.
  • Employed sodium nitroprusside (SNP) as an NO generator and reduced hemoglobin to scavenge NO.
  • Assessed the effects of SNP on the uptake of other neurotransmitters and on [3H]WIN 35428 binding to DAT.

Main Results:

  • Sodium nitroprusside (SNP) significantly decreased [3H]dopamine uptake in a dose-, time-, and temperature-dependent manner.
  • The NO scavenger reduced hemoglobin abolished the inhibitory effect of SNP, confirming NO mediation.
  • SNP also inhibited [3H]serotonin and [3H]glutamate uptake but not [3H]norepinephrine uptake, indicating some transporter selectivity.
  • Kinetic analysis revealed that SNP reduced Vmax and altered Km at higher concentrations, suggesting a functional inhibition of the dopamine transporter.

Conclusions:

  • Nitric oxide (NO) directly impairs the function of the dopamine transporter (DAT).
  • NO-induced inhibition of dopamine uptake is not due to altered drug binding to the transporter.
  • These findings highlight a novel regulatory role for NO in dopaminergic neurotransmission.

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