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Adenosine diphosphate inhibits the serotonin transporter
G M Anderson1, L M Hall, W C Horne
1Child Study Center, Yale University School of Medicine, New Haven, CT 06520-7900, USA.
Biochimica Et Biophysica Acta
|August 14, 1996
Summary
Adenosine 5'-diphosphate (ADP) significantly reduces serotonin uptake in platelets and vesicles. This rapid effect, observed in human and rat models, suggests a novel regulatory mechanism for neurotransmitter transport.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Serotonin uptake is crucial for neurotransmission.
- Adenosine 5 '-diphosphate (ADP) is a key signaling molecule in platelets and other cells.
- The precise mechanisms regulating serotonin transporter activity are not fully understood.
Purpose of the Study:
- To investigate the effect of Adenosine 5 '-diphosphate (ADP) on serotonin ([3H]serotonin) uptake.
- To characterize the kinetics and potential mechanisms of ADP-mediated inhibition of serotonin transport.
Main Methods:
- Assessing [3H]serotonin uptake rates in human platelets, human platelet vesicles, and rat brain synaptic vesicles.
- Determining kinetic parameters (Vmax, KM) and EC50 values for ADP.
- Evaluating the effect of ADP on [3H]citalopram binding to the serotonin transporter.
- Testing the effects of ADP analogues and protein kinase C (PKC) activation.
Main Results:
- ADP caused rapid and significant reductions in [3H]serotonin uptake rates across all tested models.
- Estimated Vmax values were reduced by 42.3% in platelets, 78.8% in platelet vesicles, and 56.8% in synaptic vesicles at 100 microM ADP.
- EC50 values for ADP in platelets and platelet vesicles ranged from 10-24 microM.
- ADP showed minimal and inconsistent effects on KM values and only slight competitive inhibition of [3H]citalopram binding.
Conclusions:
- Adenosine 5 '-diphosphate (ADP) potently inhibits serotonin uptake in platelets and neuronal vesicles.
- The observed effect is rapid and does not appear to involve classical ADP receptors or second messenger pathways.
- The findings suggest a novel, non-canonical mechanism by which ADP influences serotonin transporter function, warranting further investigation into its precise molecular basis and physiological relevance.