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S Sundram

Publications and source records attributed to S Sundram.

4 recordsLinked to original sources

Typical and atypical neuroleptic drugs decrease platelet 3H-dopamine uptake in the rat.

Reports of opposing changes in platelet 3H-dopamine uptake in neuroleptic-free versus neuroleptic-treated schizophrenic subjects have suggested an effect of neuroleptic treatment on this measure. We examined platelet 3H-dopamine uptake in rats treated with haloperidol or clozapine to determine if such treatment did affect platelet 3H-dopamine uptake. Neuroleptic drug treatment reduced platelet 3H-dopamine uptake in a dose- and time-dependent manner. After up to 4 weeks of treatment, these effects were reversed by the discontinuation of neuroleptic drug treatment. These data suggest that the effect of neuroleptic treatment in studies of platelet 3H-dopamine uptake could account for the variable findings in schizophrenia.

Animals

Platelet [3H]dopamine uptake is differentially affected by neuroleptic drug treatment in schizophrenia and schizophreniform disorder.

1. The uptake of [3H] dopamine was measured using platelet-rich plasma (PRP) from neuroleptic-free subjects and again, in some cases, after the subject had been treated with neuroleptic drugs. 2. There were no differences in [3H]dopamine uptake by PRP in subjects who were or were not mentally ill. 3. After treatment with neuroleptic drugs the Km for platelet [3H] dopamine uptake had increased in 76% of subjects with schizophrenia and 87% of subjects with schizophreniform disorder. Similarly, the Vmax for platelet [3H]dopamine uptake had increased in 81% of the subjects with schizophrenia and 86% of the subjects with schizophreniform disorder. 4. By contrast, the Km for platelet [3H]dopamine uptake had decreased in 94% of subjects who had a psychoses associated with an illness other than schizophrenia or schizophreniform-disorder whilst the Vmax for platelet [3H]dopamine uptake also decreased by 94% in these subjects. 5. In subjects with psychoses, platelet [(3)H] dopamine uptake is differentially altered during neuroleptic drug treatment depending on diagnosis.

Adult

The development of a method to measure [3H] dopamine uptake by washed platelets provides no evidence for circulating inhibitors of platelet dopamine uptake in schizophrenia.

Altered [3H] dopamine uptake by platelet-rich plasma (PRP) has been reported in some subjects with schizophrenia (Rotman et al 1980; Dean et al 1990). As platelet dopamine uptake was measured using PRP, it was not possible to determine if the changes in schizophrenia were intrinsic to the platelet or due to plasma factors. Furthermore, the constraints of plasma as a medium for platelet suspension has hindered the study of the physiological requirements of platelet dopamine uptake. A method is now reported that allows platelets to be suspended in a controlled medium while preserving the dopamine uptake mechanism of the platelet. Dopamine uptake by platelets in a controlled medium was dependent on temperature, energy, sodium, and chloride. Furthermore, plasma from subjects with schizophrenia and schizophreniform disorder did not significantly alter [3H] dopamine uptake by platelets compared to the effect of plasma from control subjects. Hence, these data provide no evidence for a circulating inhibitor of platelet [3H] dopamine uptake in plasma from subjects with schizophrenia.

Blood Platelets

Identification of a dopamine-binding protein on the membrane of the human platelet.

The binding of [3H]dopamine to platelet membranes has been examined in an attempt to identify the putative dopamine-uptake mechanism of the platelet. [3H]Dopamine has been shown to bind to a 42,000 Da glycoprotein in platelet membrane with high affinity (Kd = 22.6 nM) and binding of [3H]dopamine was competed for by dopamine, molecules with catechol moieties, 5-hydroxytryptamine, GSH and ascorbic acid. Differences in pharmacological profile and molecular mass suggest that [3H]dopamine does not bind to a known receptor, a neuronal-type dopamine transporter or the platelet 5-hydroxytryptamine-uptake site. It is proposed that this novel binding site for dopamine, which has been purified 1000-fold from particulate platelet membrane, is likely to be a component of the dopamine-uptake mechanism of the human platelet.

Biological Transport