Release of 5-hydroxytryptamine from blood platelets

Paasonen, M. K.

doi:10.1111/j.2042-7158.1965.tb07590.x

Cited by 84 publications

(29 citation statements)

References 76 publications

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“…As rat blood platelets do not contain monoamine oxidase (Paasonen, 1965), it was assumed that radioactivity was a measure of 5-HT uptake. Uptake of [14C1 -5-HT was calculated as described by David & Herion (1972).…”

Section: Up Take Of [14c] -5-hydroxytryptamine By Plateletsmentioning

confidence: 99%

“…The study was carried out on blood platelets, considered by several authors as a simple model for nerve endings (Paasonen, 1965;Pletscher, 1968;Tuomisto, 1974). The selected animal species was the rat as most studies of the effects of fenfluramine on 5-HT have been carried out in this species; in addition, rat platelets are unable to metabolize 5-HT (Paasonen, 1965).…”

Section: Introductionmentioning

confidence: 99%

“…The selected animal species was the rat as most studies of the effects of fenfluramine on 5-HT have been carried out in this species; in addition, rat platelets are unable to metabolize 5-HT (Paasonen, 1965).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Fenfluramine on 5‐hydroxytryptamine Uptake and Release by Rat Blood Platelets

Buczko

Gaetano

Garattini

1975

British J Pharmacology

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(+)‐Fenfluramine reduces the central stores of 5‐hydroxytryptamine (5‐HT) by a poorly understood mechanism. Rat blood platelets have been used in this study as a simple model for serotoninergic nerve endings. (+)‐Fenfluramine shows a dual effect: it inhibits the uptake of [14C]‐5‐HT by platelets and it releases newly absorbed [14C]‐5‐HT from platelets. The inhibition of [14C]‐5‐HT uptake induced by (+)‐fenfluramine appears very rapidly, is concentration‐dependent and seems not to be competitive. (+)‐Fenfluramine is ten times less effective than chloroimipramine but ten times more effective than (+)‐amphetamine; (+)‐fenfluramine is more active than its (‐)‐isomer or its metabolite norfenfluramine ((+)‐ or (‐)‐form). The release of [14C]‐5‐HT from platelets induced by (+)‐fenfluramine is concentration‐dependent but increases with increased incubation time. Both chloroimipramine and (+)‐amphetamine are in comparison very poor release inducers; (+)‐fenfluramine is more active than its (‐)‐isomer or its metabolites. The effect on [14C]‐5‐HT uptake exerted by (+)‐fenfluramine and chloroimipramine in vitro could not be observed in vivo. The observed effect of fenfluramine on the uptake and release of 5‐HT may explain the lowering action of fenfluramine on the brain 5‐HT level, an effect considered of importance for the anorectic effect of this drug.

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Section: Up Take Of [14c] -5-hydroxytryptamine By Plateletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Fenfluramine on 5‐hydroxytryptamine Uptake and Release by Rat Blood Platelets

Buczko

Gaetano

Garattini

1975

British J Pharmacology

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“…It was thought that platelets do not synthetize 5-hydroxytryptamine (Paasonen, 1965) but recently 5-hydroxytryptophan decarboxylase activity has been demonstrated in vitro in extracts of human and beef platelets (Marmaras & Mimikos, 1971 responsible for the accumulation of 5-hydroxytryptamine (5-HT) in cytoplasmic organelles; specifically that 5-HT forms a stable complex with adenosine triphosphate (Born, Ingram & Stacey, 1958;Da Prada & Pletscher, 1968;Pletscher, Da Prada & Tranzer, 1969). Most of this stored 5-HT is released together with adenosine triphosphate (ATP), by aggregating agents such as thrombin (Grette, 1962), adenosine diphosphate (ADP) and collagen (Packham, Guccione, Chang & Mustard, 1973).…”

Section: Introductionmentioning

confidence: 99%

Shape Change and Aggregation of Blood Platelets: Interaction Between the Effects of Adenosine Diphosphate, 5‐hydroxytryptamine and Adrenaline

Michal¹,

Motamed²

1976

British J Pharmacology

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I The interaction of effects between 5-hydroxytryptamine (5-HT) and adenosine diphosphate (ADP) on human or rabbit platelets was investigated in vitro. The initial platelet shape change and their aggregation were measured in stirred, citrated platelet-rich plasma (PRP) at 37°C by recording the rate and extent of changes in light scattering and light transmission. 2 Both the velocity and extent of aggregation and the velocity and extent of the rapid morphological change caused by ADP were enhanced by simultaneous addition of 5-HT. Methysergide but not imipramine inhibited the 5-HT effects. 3 Platelets were made refractory to the aggregating and shape changing effect of either ADP or 5-HT by repeated aggregation with the particular agent; platelets made refractory to ADP retained their responsiveness to 5-HT and platelets made refractory to 5-HT responded to ADP. Platelets pre-incubated for 3-10 min with 5-HT without aggregation showed greatly reduced aggregation on subsequent addition of ADP. Methysergide inhibited all the effects of 5-HT whilst imipramine was inactive. 4 When the shape change or aggregation of platelets induced by ADP was submaximal, addition of 5-HT increased it further. Pre-incubation of PRP with 5-HT before the addition of ADP resulted in failure of the secondary induction of aggregation or shape change by 5-HT. The secondary induction by 5-HT also did not occur in the presence of methysergide; imipramine had no inhibitory effect. Similar secondary induction of aggregation was shown by adrenaline injected during aggregation by ADP; the adrenaline effect was removed by phentolamine but not by propranolol. 5 Our results show that the initial change in shape of platelets and their aggregation can be induced by ADP or 5-HT in specific manner. The interaction of the effect of these substances on platelets can result in either increase in platelet sensitivity or, under certain conditions, decrease in platelet responsiveness. The increase or depression of platelet reactivity appears to be a highly specific effect and is probably mediated at specific receptors involved with platelet activation.

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“…There is considerable evidence that platelets may serve as model systems for uptake, binding, and release of neurotransmitter monoamines in nerve endings in the brain and the peripheral nervous system (1)(2)(3). Reuptake into the presynaptic neuron of released neurotransmitter is the most important step in controlling the intrasynaptic concentration and neural effects of monoamine neurotransmitters (4,5).…”

Section: Introductionmentioning

confidence: 99%