5‐hydroxytryptamine in normal human platelets

Hardisty, R. M.; Stacey, R. S.

doi:10.1113/jphysiol.1955.sp005437

Cited by 176 publications

(71 citation statements)

References 11 publications

(13 reference statements)

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“…The uptake of noradrenaline or serotonin by thrombocytes and other tissues in vitro and in vivo was confirmed by many authors (13)(14)(15)(16). If the restarting and excitatory effects of the amines on the action potential were derived from the uptake of the amines by the tissue, reserpine in vitro may depress the uptake of adrenaline or noradrenaline more markedly than reserpine in vivo.…”

Section: Discussionmentioning

confidence: 49%

The Mode of Action of Reserpine on the Transmembrane Potential of Rabbit’s Atrium in Vitro

Toda

1962

Japanese Journal of Pharmacology

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Section: Discussionmentioning

confidence: 49%

The Mode of Action of Reserpine on the Transmembrane Potential of Rabbit’s Atrium in Vitro

Toda

1962

Japanese Journal of Pharmacology

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“…0.7% w/v sodium chloride solution). The separation of platelet-rich plasma was carried out according to the technique described by Hardisty & Stacey (1955) and Stacey (1961).…”

Section: Methodsmentioning

confidence: 99%

“…0.7% w/v sodium chloride solution). The separation of platelet-rich plasma was carried out according to the technique described by Hardisty & Stacey (1955) and Stacey (1961).Incubation experiments with radioactive guanethidine The procedure used was based on that described by Stacey (1961), with the following modifications: 1.2 ml. platelet-rich plasma, mixed with 0.3 ml.…”

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confidence: 99%

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The accumulation of guanethidine by human blood platelets

Boullin

O'Brien

1969

British J Pharmacology

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1. When human blood platelets were incubated aerobically in plasma containing 2 x 10-7 to 10-3M radioactive guanethidine for 10 min to 6 hr, the drug was accumulated against a concentration gradient until concentration ratios (platelet/plasma) of up to 80: 1 were obtained. 2. The decline in rate of uptake after 3 hr appeared to result from a decrease in platelet viability, because accumulation was reduced by prolonged incubation before addition of guanethidine. 3. Uptake was energy-dependent because it was inhibited by cold and ouabain. 4. Sodium ions were essential for guanethidine uptake and retention of 5-hydroxytryptamine (5-HT). 5. Accumulation was inhibited by 5-HT, desipramine, cocaine, dexamphetamine, bretylium, tyramine and noradrenaline; bethanidine, p-chlorophenylalanine and (-)-a-methyldopa were inactive. 6. Guanethidine was tightly bound to platelets, only 10% being lost from labelled cells during 60 min incubation in drug-free plasma; but efflux was increased by addition of amphetamine. 7. The binding sites for guanethidine seemed to be different from those for 5-HT since guanethidine accumulation was independent of 5-HT levels, and neither guanethidine uptake or release were affected by reserpine. 8. Guanethidine was not metabolized by platelets or plasma in vitro. 9. We consider that, if our results regarding uptake, binding and release of guanethidine are confirmed in vivo, and also found to apply to other pharmacologically active agents, then the eventual loss of a platelet-bound substance may increase pharmacological action by raising plasma levels.Although there is considerable information concerning the mechanisms of uptake and sites of storage of 5-hydroxytryptamine (5-HT) and noradrenaline (NA) by blood platelets, the fact that platelets can also accumulate a wide variety of other substances such as procaine, histamine, reserpine, quinidine, amino-acids, sugars Guanethidine uptake by platelets and diuretic drugs has only recently been demonstrated (Solomon & Zieve, 1967;Zieve & Solomon, 1967.Recent work indicates that in several respects the blood platelet resembles the sympathetic nerve ending. Although 5-HT is the'predominant amine in platelets and sympathetic nerves contain only NA, both structures preferentially accumulate the respective amine by an energy-dependent mechanism and store it in sub-cellular vesicles which show a dense core under the electron microscope (for references see Potter, 1967;Pletscher, 1968). As the uptake of guanethidine by sympathetic nerves is well established (for references see Boullin, 1968), it was thought that blood platelets might also take up guanethidine. This paper shows that this is the case: guanethidine is concentrated to a considerable degree by an energy-dependent process. As the ratio of the concentration of guanethidine in platelets to that in the incubation medium may exceed 50: 1, the possibility that platelet-bound guanethidine may be of clinical significance is discussed.Some of these experiments have been reported in preliminary communica...

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“…Although it has been known for many years that platelets accumulate 5-hydroxytryptamine (5-HT) (Humphrey & Toh, 1954; Hardisty & Stacey, 1955) and noradrenaline (Born & Hornykiewicz, 1957;Born, Hornykiewicz & Stafford, 1958), the accumulation of dopamine has not been investigated. Recently have demonstrated the uptake of dopamine by the subcellular 5-HT storage organelles isolated from rabbit platelets.…”

Section: Introductionmentioning

confidence: 99%

Accumulation of dopamine by blood platelets from normal subjects and parkinsonian patients under treatment with l‐DOPA

Boullin

O'Brien

1970

British J Pharmacology

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Summary ,1. Human blood platelets have been shown to take up dopamine by an energydependent, saturable process that is inhibited by 5-hydroxytryptamine (5-HT), desipramine and other drugs. 2. Platelets from parkinsonian subjects receiving oral L-DOPA also took up dopamine.3. When the responses of normal and parkinsonian platelets were compared, the parkinsonian cells showed the following differences: increased affinity for the dopamine transport process; decreased equilibrium concentrations of dopamine after incubation for 90 min, and greater efflux of dopamine from loaded platelets during a 10 min incubation. 4. There were no differences in the uptake of 5-HT by parkinsonian platelets, but endogenous 5-HT was significantly reduced; ATP was normal. 5. In two out of three samples of platelets from parkinsonian subjects, traces of a dopamine-like substance were detected, but this finding requires confirmation. 6. If the platelet is a valid model for dopaminergic brain neurones, then the results described would suggest that dopamine uptake and storage may be abnormal in brain neurones in Parkinson's disease.

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5‐hydroxytryptamine in normal human platelets

Cited by 176 publications

References 11 publications

The Mode of Action of Reserpine on the Transmembrane Potential of Rabbit’s Atrium in Vitro

The Mode of Action of Reserpine on the Transmembrane Potential of Rabbit’s Atrium in Vitro

The accumulation of guanethidine by human blood platelets

Accumulation of dopamine by blood platelets from normal subjects and parkinsonian patients under treatment with l‐DOPA

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