Abnormalities of 5‐hydroxytryptamine uptake and binding by blood platelets from children with Down's syndrome

Boullin, D. J.; O'Brien, R.A.

doi:10.1113/jphysiol.1971.sp009325

Cited by 82 publications

(23 citation statements)

References 18 publications

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“…As this paper was being prepared for publication, Boullin and O'Brien [6] reported results that are in agreement with our findings of low content of 5HT in platelets, and defective uptake of the amine by mongol platelets. In addition, they observed an increased rate of 14 C-5HT efflux from mongol platelets which was associated with a low ATP concentration.…”

Section: Addendumsupporting

confidence: 80%

Down's Syndrome: Transport, Storage, and Metabolism of Serotonin in Blood Platelets

1972

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ExtractSerotonin (5HT) transport and metabolism were studied in platelets from 14 trisomy-21 patients who were matched with 12 sibling and 9 non-sibling control subjects with regard to age, sex, home environment, diet and weight. Endogenous 5HT content, in nanograms per milligram platelet protein, was reduced from 446 ± 66 in the sibling controls and from 492 ± 74 in the non-sibling controls to 158 ± 16 in the Down's syndrome group, a difference of 61% and 68% respectively (P < 0.001). Initial uptake of l4 C-5HT measured after a 3-min incubation period was reduced 35% (P < 0.05) in the platelets from Down's syndrome patients, while the efflux of radiolabeled amine from platelets was not significantly altered in these patients. Since platelets do not synthesize 5HT, the decreased transport found may explain the lower 5HT levels in these patients. Mongols did not differ from control subjects in the activity of platelet monoamine oxidase. SpeculationSimilarities in the uptake, storage, and release of 5HT between the human blood platelet and the serotonergic neuron suggest that the 5HT abnormality observed in mongol platelets may reflect disordered metabolism of the monoamine within the central nervous system.

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Section: Addendumsupporting

confidence: 80%

Down's Syndrome: Transport, Storage, and Metabolism of Serotonin in Blood Platelets

1972

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“…Additional experiments in which we measured the change in the total 5-HT (endogenous + 14C-5-HT) and ATP caused by quinidine from 14C-5-HT loaded platelets are summarized in Table 3. The molar ratio of ATP to 5-HT of 2-38 to 1 in these loaded cells is between the value of 1P79 to 1 found by Boullin & O'Brien (1970) in children, and 3'23 to 1 found by Born, Ingram & Stacey (1958) for adults. The quantity of 5-HT released represented 61-4% endogenous and 57% exogenous amine, there being no change in the ratio of exogenous to endogenous indolealkylamine.…”

Section: Effects Of Quinidine On S-ht and Atpmentioning

confidence: 94%

Accumulation of quinidine by human blood platelets: effects on platelet ultrastructure and 5‐hydroxytryptamine

Boullin

O'Brien

1971

British J Pharmacology

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Summary1. We have studied the mechanism of quinidine uptake by normal human blood platelets. 2. Platelets in plasma or Krebs solution took up quinidine extremely rapidly, the maximal drug concentration ratio of platelet to medium being 24 to 1 after 1 minute. 3. The effects of metabolic inhibitors on uptake were equivocal. Ouabain had no effect but iodoacetate and dinitrophenol were effective. However, as accumulation was not inhibited by low temperature, it was probably not energy dependent. 4. Interactions between quinidine and 5-HT were also investigated. 5. Quinidine blocked 5-HT uptake, but conversely, neither 5-HT itself nor 5-HT uptake inhibitors, such as cocaine, dexamphetamine, and desipramine interfered with quinidine accumulation. 6. Electronmicrographs of platelets incubated with 10-5, 10-4 or 2 x 10-3M quinidine in Krebs solution for 2 h showed no changes at the lower concentrations, but gross ultastructural damage, including disintegration of the plasma membrane, at 2 x 10-3M.7. Further evidence for intracellular penetration was obtained because quinidine released endogenous 5-HT and ATP, and also 14C-5-HT from loaded cells. 8. We conclude that quinidine is taken up by the platelet by a passive process, unrelated to the 5-HT transport mechanism. It is probably accumulated largely in the plasma membrane and outer protein layer, but intracellular penetration and ultrastructural damage may occur.9. Although the effects on 5-HT and ATP were not due to platelet damage, this may occur in vivo and be the cause of quinidine induced thrombocytopenic purpura.

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“…Other possible contributory causes with regard to the low platelet serotonin content are defective synthesis by enterochromaffin cells in the gastro-intestinal mucosa and increased metabolism by platelet monoamine oxidase. (Boullin, 1971). Several authors have observed that in the blood of patients with Down's syndrome 5-HT is reduced (Rosner, 1965;Tu, 1965;Jerome, 1967) because of a possible defect in serotonin transport and have suggested that, if platelets are a valid model for serotoninergic neurons, any changes observed in platelets should imply similar possible effects within the brain.…”

Section: Serotonin In Enterochromaffin Cells and Plateletsmentioning

confidence: 99%

The Interactome Hypothesis of Depression

et al. 2010

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It has long been known that the most important function of platelets is to stop the flow of blood from wounds with the help of a set of enzymes, proteins, and lipids supporting complex metabolic clot-forming mechanisms. It is also known that there are close correlations, both enzymatic and metabolic, between platelets and nerve cells with respect to the metabolism of several neurotransmitters such as serotonin, dopamine, GABA, etc. Platelets, which serve an historic role as biological markers in psychiatry, can in fact be regarded as virtual "circulating neurons" or "brain ambassadors" that may offer a significant advantage in understanding the neurophysiology of psychiatric disorders including depression. Critical points of potential specific linkage between platelets and depression include serotonin and membrane platelet fatty acids in relation to the cytoskeletal quantum-nanowire network. This paper advances an "interactome" hypothesis of possible connections among enterochromaffin cells, serotonin, platelets and cytoskeletal proteins related to brain neurons with implications regarding the genesis of depressive psychopathology.

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Abnormalities of 5‐hydroxytryptamine uptake and binding by blood platelets from children with Down's syndrome

Cited by 82 publications

References 18 publications

Down's Syndrome: Transport, Storage, and Metabolism of Serotonin in Blood Platelets

Down's Syndrome: Transport, Storage, and Metabolism of Serotonin in Blood Platelets

Accumulation of quinidine by human blood platelets: effects on platelet ultrastructure and 5‐hydroxytryptamine

The Interactome Hypothesis of Depression

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