The human platelet as a pharmacologic model for the adrenergic neuron

Abrams, William B.; Solomon, Harvey M.

doi:10.1002/cpt1969105702

Cited by 87 publications

(26 citation statements)

References 17 publications

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“…The active uptake of 5-hydroxytryptamine (5-HT) into blood platelets and the effect of pharmacological agents thereon have been studied intensively, (Pletscher, 1968;Paasonen, 1972), because it can be more closely controlled experimentally than most other active transport systems for amines and because of the possible significance of blood platelets as a model of the nerve ending with respect to its amine re-uptake system (Maynert & Isaac, 1968 ;Murphy, Colburn, Davis & Bunney, 1970;Abrams & Solomon, 1970). This uptake is blocked by low concentrations of tricyclic anti-depressive drugs (Todrick & Tait, 1969) which, however, have negligible actions on many enzyme systems (L0vtrup, 1963, 1964).…”

Section: Introductionmentioning

confidence: 99%

On the pharmacology and biochemistry of the amine‐uptake mechanism in human blood platelets

Campbell

Todrick

1973

British J Pharmacology

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Summary1. The uptake of 5-hydroxytryptamine (5-HT) by human blood platelets in vitro has been studied with the object of identifying the biochemical mechanisms involved.2. Drugs active in adrenergic systems are only moderate inhibitors of uptake, although prenylamine is as active as the less potent tricyclic anti-depressive drugs; phenoxybenzamine is almost inactive as a competitive inhibitor but is effective if pre-incubated with the platelets beforehand. This parallels its pharmacological pattern of action. 3. Inhibitors of oxidative phosphorylation do not inhibit 5-HT uptake, but iodoacetate inhibits, if pre-incubated with the platelets; p-chloromercuribenzoate does also, when the platelets are suspended in synthetic medium, but not in plasma.4. Ouabain causes significant inhibition at 10-7M; by 10-6M it achieves its maximal effect, namely 40% inhibition; in K+-deficient medium, uptake falls to 30% of normal; the K+-dependent fraction of the uptake includes the ouabain-sensitive component. Mg++ has no effect. 5. A drug not possessing the imipramine structure, which has been tried in the treatment of depressive illness, 4-phenyl bicyclo (2,2,2) octan-l-amine, is a highly potent inhibitor of 5-HT uptake.

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Section: Introductionmentioning

confidence: 99%

On the pharmacology and biochemistry of the amine‐uptake mechanism in human blood platelets

Campbell

Todrick

1973

British J Pharmacology

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“…Intact human platelets can be employed to test uptake mechanisms for NE (12). The platelets are capable of functioning in appropriate conditions and actively taking up NE from the medium in concentrations up to 10 ,ug/liter (26).…”

Section: Discussionmentioning

confidence: 99%

“…Five patients with AIP had low URO-S levels, a characteristic abnormality in this disease (21), whereas all controls had normal values. The one patient with HC manifested a level of urinary coproporphyrin diagnostic of this disease during an acute exacerbation (22) (12) and found to produce a significant inhibition of [3H]NE uptake into platelets obtained from both groups.…”

Section: Introductionmentioning

confidence: 98%

“…The isolated perfused rat heart was chosen because of its convenience for in vitro studies to determine whether ALA and PBG have a direct toxic effect on catecholamine metabolism. Studies were also performed on normal human platelets and platelets of patients with acute porphyria, because platelets are able to accumulate and store catecholamines by a process which resembles that of adrenergic neurons (12)(13)(14) (15). The normal perfusion medium contained 119.8 mM NaCl, 5.63 mM KC1, 2.16 mM CaC12, 2.10 mM MgCl2, 100 mM dextrose, and 25 mM NaHCO3.…”

Section: Introductionmentioning

confidence: 99%

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Catecholamine Uptake, Accumulation, and Release in Acute Porphyria

Beal¹,

Atuk²,

Westfall³

et al. 1977

J. Clin. Invest.

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A B S T R A C T Hypertension and tachycardia are well known features of acute porphyria and have been shown to be related to increased circulating catecholamines. The mechanism by which circulating catecholamines are increased was studied using the isolated perfused rat heart and human platelets as a model of adrenergic neuronal function. It was found that neither 8-aminolevulinate (ALA) nor porphobilinogen (PBG) blocked uptake or caused release in the isolated perfused rat heart. Platelets from six patients with acute prophyria, three in remission and three latent, with matching normal controls were studied with regard to their uptake of [3H]

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“…Explanations for this biochemical abnormality have included alterations in the metabolism of 5HT [11,14] or in the uptake, storage, or release [4,13] of the amine by blood platelets, the cellular structures which contain virtually all the 5HT present in whole blood [22,28]. The possibility that low levels of 5HT in platelets relate to the central nervous system defect in Down's syndrome is suggested by recent evidence that the human platelet has certain structural and functional similarities to amine-containing neurons [1,[19][20][21]. On the assumption that the whole blood abnormality of 5HT in Down's syndrome may reflect defective metabolism of this putative neurotransmitter amine in the central nervous system, L-5-hydroxytryptophan, the immediate precursor of 5HT, has been administered to neonatal mongols and has been shown to produce some alteration in neuromuscular function [2].…”

Section: Introductionmentioning

confidence: 99%

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 14 G-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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The human platelet as a pharmacologic model for the adrenergic neuron

Abstract: The uptake and release of norepinephrineThe uptake of norepinephrine (NE)

Cited by 87 publications

References 17 publications

On the pharmacology and biochemistry of the amine‐uptake mechanism in human blood platelets

On the pharmacology and biochemistry of the amine‐uptake mechanism in human blood platelets

Catecholamine Uptake, Accumulation, and Release in Acute Porphyria

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

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