Human Platelet Serotonin Research Articles

Inhibitory Effect of Ethanol on 5‐Hydroxytryptamine (Serotonin) Uptake in Human Blood Platelets in Vitro

Ethanol in concentrations higher than 10(-2) M (or about 0.5% W/W) inhibited the uptake of 14C-5-hydroxytryptamine (serotonin) in human blood platelets in an artificial, protein-free medium, by a non-competitive mechanism. The inhibition was not influenced by the alcohol dehydrogenase inhibitor methylpyrazole (10(-3) M). In concentrations up to 0.1 M, ethanol had no effect on 5-HT efflux from the platelets. At higher concentrations, ethanol increased efflux. Inhibition of 5-HT uptake was found to increase progressively in the sequence methanol - ethanol - propanol - butanol.

Contributions cliniques et biochimiques sur l’action de la maprotiline et de la clomipramine dans les états dépressifs

This study has been conducted on 17 patients suffering from neurotic and psychotic depressions, who had not received a pharmacological antidepressive therapy since at least 1 month. 6 patients suffering from psychotic depression were treated with 100 mg clomipramine i.v. daily for 20 days; 11 patients, 7 of whom suffered from psychotic depression and 4 from neurotic depression, were treated with 150 mg maprotiline i.v. daily for 20 days. In both groups the therapy has been continued orally. In 17 patients a remarkable improvement and even in some cases complete recovery has been obtained. The two psycho-tropic antidepressive drugs are, furthermore, both active in the same symptoms. The determination of serotonin in human platelets confirms the strong inhibition of its re-uptake by clomipramine and the absence of re-uptake of 5-HT with maprotiline. A constant and progressive increase of 5-HIAA was noted in patients treated with clomipramine. This increase may be considered as a consequence of the increased metabolism of the larger quantity of 5-HT used by the central synapses. The interpretation of the increased levels of 5-HIAA in patients treated with maprotiline is more difficult. Further trials, for instance on the plasmatic tryptophan level, will perhaps solve the problem.

Mechanisms of cellular interaction with monosodium urate crystals. IgG-dependent and IgG-independent platelet stimulation by urate crystals.

Monosodium urate crystals (MSU) stimulate suspensions of washed platelets or neutrophils. When MSU crystals are coated with IgG, as occurs in plasma, stimulation is markedly enhanced. These studies which use MSU-induced human platelet serotonin secretion as a model examine the nature of cellular recognition mechanisms for MSU crystals and IgG-coated MSU crystals. F(ab')2 fragments of specific anti-Fc antibody blocked and the lipopolysaccharide of Salmonella minnesota R595 enhanced human platelet secretion induced by IgG-coated urate crystals. These agents had little effect on stimulation by uncoated crystals. This indicated that urate crystals stimulate platelets independently of fluid phase IgG. Urate crystals directly stimulated suspensions of washed rabbit platelets which lack Fc receptors. In contrast to human cells, stimulation was blocked by IgG. This again demonstrated IgG-independent cell stimulation by urate crystals. Calcium pyrophosphate dihyrate crystals could trigger human platelet secretion only when coated with IgG. This suggests that when crystals are coated with IgG, the surface-bound IgG alone may be the stimulus to the cell. This was supported by the finding that polyvinylpyridine-N-oxide, a hydrogen acceptor, blocked human platelet stimulation by uncoated, but not IgG-coated, urate crystals. These data indicate that urate crystals (and potentially other surface or particles) can stimulate a mediator cell by at least two mechanisms: by direct stimulation without the mediation of adsorbed IgG or, when coated with IgG, by triggering the cell via immunoglobulin receptors.

A common uptake system for serotonin and dopamine in human platelets.

Kinetic and pharmacologic properties of uptake of serotonin and dopamine by normal human platelets have been investigated to test whether platelets can be employed as a model system for the reuptake of serotonin and dopamine in brain. Uptake of serotonin into platelets closely resembles reuptake of serotonin into serotonergic neurons. In contrast, uptake of dopamine into platelets appears to be mediated inefficiently via the specific serotonin uptake mechanism, based upon several lines of evidence. Serotonin and dopamine compete with each other, Antidepressant drugs, which are competitive inhibitors of uptake of both of these neurotransmitters, act at the same concentration of drug despite large differences in the Km values. Serotonin antagonists inhibit both serotonin and dopamine uptake. Finally, a serotonin-specific uptake inhibitor (fluoxetine) blocks dopamine, as well as serotonin, uptake.

Effects of antimycin a plus 2-deoxyglucose on uptake and vesicular storage of serotonin in human platelets

The effects of the metabolic poisons antimycin A (4.1 μg/ml) and 2-deoxyglucose (32.2 mM) on the uptake and vesicular storage of serotonin in washed human platelets have been examined. Within 15 seconds after the addition of the metabolic poisons, H 3-5HT begins to move from vesicles into the cytoplasm; by 30 minutes after poison addition, essentially all the platelet 5HT appears to be cytoplasmic. The metabolic poisons also act rapidly to decrease plasma-membrane uptake of H 3-5HT from the extracellular medium by approximately 20% within 1 minute after their addition. This may represent a direct effect rather than one resulting from altered cytoplasmic or vesicular 5HT, since platelets with <10% of the normal number of vesicular storage sites exhibit a similar reduction after addition of the metabolic poisons.

On the Interrelationship of Prostaglandin Endoperoxide G2 and Cyclic Nucleotides in Platelet Function

The prostaglandin endoperoxide G2 caused rapid aggregation and relase of ADP and [14C]serotonin in human platelets. Since the presence of the ADP phosphorylating system creatine phosphate/creatine phosphokinase markedly inhibited the aggregation caused by the endoperoxide, this effect seemed to be mediated mainly by ADP, which is instantaneously released by the endoperoxide. The prostaglandin G2 counteracted the increasing effect of prostaglandin E1 on the adenosine 3':5'-monophosphate (cAMP) levels in platelet-rich plasma. This effect of prostaglandin G2 was only observed when ADP was released by the endoperoxide. This finding indicates that the effect of prostaglandin G2 on the cAMP levels in platelet-rich plasma is principally mediated by ADP. The rapid release of ADP by prostaglandin G2 and the time courses for the effects of the endoperoxide and ADP on the level of cAMP give further evidence for this hypothesis. ADP also caused primary aggregation in the presence of indomethacin, and prostaglandin synthesis inhibitors did not influence the decreasing effect of ADP on the cAMP levels. N2,O2-Dibutyrylguanosine 3':5'-monophosphate did not influence the aggregation and release-reaction caused by ADP and no changes of the cGMP levels were observed after addition of prostaglandin G2.

Diurnal and seasonal variations in human platelet serotonin in man.

Platelet serotonin (5-HT) was found to be an individually constant parameter correlating with the uptake of exogenous 5-HT. A pronounced diurnal pattern of 5-HT, with a minimum in the afternoon and higher values in the morning and evening, was similar to the diurnal variations in plasma free tryptophan. Platelet 5-HT was significantly higher at 8 a.m. than 4 p.m. in spring but no longer in autumn, and was similar in both men and women. It appeared that peripheral diurnal variations in 5-HT were opposite in phase to the central 5-HT rhythm.

Subcellular Localization of Fluorinated Serotonin in Human Platelets by Electron Energy-Loss Spectroscopy

Fluorinated organic molecules have considerable potential as tracers in bio logical systems, since a number of fluorinated analogs demonstrate biological activity similar to that of the parent molecule1. To date, however, the subcellular localization of fluorine has been hampered by the relatively low sensitivity of conventional X-ray microanalysis systems to fluorine. Electron energy-loss spectroscopy, in contrast, is a very efficient method for detecting light elements. We have capitalized on the high sensitivity of this technique to fluorine to identify and localize fluorinated serotonin at a subcellular level in human platelets.Intact human platelets were incubated with 10-5 M concentrations of either serotonin (5HT) or 4,6 difluoroserotonin (DF5HT)2 for 30 minutes at 37°C. Following the incubation period, air-dried whole mounts3 were prepared on 200 mesh copper grids coated with collodion and carbon. Individual platelets were examined at 80 kv in the STEM mode (10 nm spot size), utilizing a Jeol 100B microscope equipped with a field emission gun, a scanning attachment, an electron spectrometer, and a Kevex analysis recording system.

Depletion of Platelet Amine Storage Granules by the Antithrombotic Agent, Suloctidil

Suloctidil, a compound with antithrombotic properties in animal models, causes depletion of human platelet serotonin stores during 1-5 hr incubation with platelet-rich plasma in vitro. This effect is not attended by leakage of cytoplasmic nucleotides or by alterations in cyclic AMP metabolism, malondialdehyde production or energy balance. 5HT uptake was also inhibited but uptake of adenine was not. 5HT released by suloctidil appeared in the supernatant as oxidation products, though the amine also accumulated when re-uptake was blocked by imipramine.

Alterations in Human-Platelet Serotonin Uptake Following the Addition of Thrombin or A 23187

Alterations in Human-Platelet Serotonin Uptake Following the Addition of Thrombin or A 23187

Cationic proteins of human granulocytes Effects on human platelet aggregation and serotonin release

Immune-aggregate and thrombin-mediated [(3)H]serotonin release from human platelets are shown to be enhanced when platelets are preincubated with the antibacterial chymotrypsin-like cationic protein isolated from human granulocytes. The enhancement is dose dependent and inhibited by heating of the cationic protein. Release with chymotrypsin-like cationic protein alone was not observed, although the protein was shown to "micro-aggregate" platelets irreversibly by an ADP-dependent reaction. Platelet "macro-aggregation" induced by immune-aggregate was also enhanced by chymotrypsin-like cationic protein whereas platelet "macro-aggregation" induced by thrombin was inhibited competitively. Platelet "micro-aggregation" induced by chymotrypsin-like cationic protein was inhibited when preincubated for more than 5 min with a 2-fold molar excess ofα-1-antitrypsin. Chymotrypsin-like cationic protein interaction with several platelet reactions suggests a close relationship between neutrophils and platelets in the inflammatory process.

Effects of serotonin uptake inhibitor, Lilly 110140, on transport of serotonin in rat and human blood platelets

Effects of serotonin uptake inhibitor, Lilly 110140, on transport of serotonin in rat and human blood platelets

Impairment of Human Platelet Aggregation and Serotonin Release Caused in Vitro by Echis Colorata Venom

SummaryAggregation of washed human platelets, induced by either ADP, thrombin or collagen, was decreased by Echis colorata venom (EVC). With ADP as an inducer, the inhibition of aggregation was proportional to the venom concentration, starting from 0.27 μg/ml and attaining full inhibition with venom concentration of 9 μg/ml. Higher concentrations were required for comparable venom effects when collagen or thrombin were used as inducers. Based on serotonin release measurements and platelet counting, it is concluded that the ECV-diminished aggregation is not due to platelet lysis. Thrombin-dependent serotonin release was inhibited by the venom to an extent proportional to the log ECV concentration at a range of 0.27 to 90 μg/ml. ECV effeces on serotonin release are apparently independent on its effects on aggregation, since similar results were obtained either with or without EDTA.Endothelial damage and defibrination are already known to be associated with the bleeding tendency caused by ECV. The present data disclose a functional impairment of platelets as an additional antihemostatic effect of this venom.

Uptake of serotonin in blood platelets in vitro. 3. Effects of acetate and other monocarboxylic acids.

AbstractThe chloride‐dependent uptake of serotonin in human blood platelets is stimulated by acetate, maximal effect being obtained with about 10–15 mM acetate at pH 7.3. In the absence of chloride (or other halogen anions), acetate has no effect on serotonin uptake. The stimulatory effect of acetate seems to be mainly due to an increased affinity of the “anionic site” of the 5HT carrier for chloride. Acetate conceiveably reacts with the hypothetical “activating site” on the plasma membrane in the same way as was previously shown to be the case for nitrite. The specific activating effect of both acetate and nitrite is blocked by increasing the extracellular potassium concentration to about 30 mM. At pH 6.2, acetate in concentrations higher than about 10 mM exerts an uncompetitive inhibitory effect on serotonin uptake. This effect is not counteracted by potassium, and seems to be quite independent of the stimulatory effect. The stimulatory effect of acetate on serotonin uptake is shared by other monocarboxylic acids, such as formate, propionate, butyrate, lactate, and pyruvate. The possibility that lactate may act as a physiological regulator of serotonin uptake in platelets and “serotoninergic” neurons is mentioned.

Quantity, assay and release of serotonin in human platelets.

ARTICLESQuantity, Assay and Release of Serotonin in Human PlateletsMarjorie B. Zucker, and Jennie BorrelliMarjorie B. Zucker, and Jennie BorrelliPublished Online:01 Jan 1955https://doi.org/10.1152/jappl.1955.7.4.425MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByComparison of serum serotonin and serum 5-HIAA LC-MS/MS assays in the diagnosis of serotonin producing neuroendocrine neoplasms: A pilot studyClinica Chimica Acta, Vol. 482Melatonin Anticancer Effects: Review24 January 2013 | International Journal of Molecular Sciences, Vol. 14, No. 2Prostacyclin inhibits 5-hydroxytryptamine release but stimulates thromboxane synthesis during cardiopulmonary bypassProstaglandins, Vol. 25, No. 4Serotonin uptake in Schistosomules of Schistosoma mansoniComparative Biochemistry and Physiology Part C: Comparative Pharmacology, Vol. 63, No. 2The influence of metabolites on the assay of platelet serotoninThrombosis Research, Vol. 10, No. 6Responsiveness of Isolated Cerebral and Peripheral Arteries to Serotonin, Norepinephrine, and Transmural Electrical StimulationCirculation Research, Vol. 33, No. 1Determination of serotonin in blood using an ion-exchange resinClinica Chimica Acta, Vol. 9, No. 5Untersuchungen �ber die Freisetzung von Serotonin aus Blutpl�ttchen durch ThrombinNaunyn-Schmiedebergs Archiv f�r Experimentelle Pathologie und Pharmakologie, Vol. 249, No. 2Hyperkinemia and cardiac failure in the carcinoid syndromeThe American Journal of Medicine, Vol. 32, No. 6FREE SEROTONIN IN HUMAN PLASMAThe Lancet, Vol. 277, No. 7177Raynaud's Disease, Raynaud's Phenomenon, and Serotonin2 July 2016 | Angiology, Vol. 11, No. 3Relationship of Platelet Serotonin to Disturbances of Clotting and HemostasisCirculation, Vol. 15, No. 3 More from this issue > Volume 7Issue 4January 1955Pages 425-431 https://doi.org/10.1152/jappl.1955.7.4.425PubMed13233134History Published online 1 January 1955 Published in print 1 January 1955 Metrics