Correlation Between Noradrenaline Fluxes, Metabolism and Compartmentalisation in Human Platelets

1982 ◽  
Vol 48 (01) ◽  
pp. 062-066 ◽  
Author(s):  
Chantal Legrand ◽  
Véronique Dubernard ◽  
Philippe Meyer
Keyword(s):  
Noradrenaline Release ◽  
Human Platelets ◽  
Release Of Noradrenaline ◽  
Storage Pool ◽  
Platelet Storage ◽  
Efflux Of Noradrenaline ◽  
Preferential Localization

Summary(3H) noradrenaline was taken up by human platelets and partially converted into sulfoconjugated noradrenaline. This uptake was inhibited by drugs which have been previously shown to impair the uptake of 5-HT (ouabain, chlorimipramine) or the storage of 5-HT (tyramine, reserpine) by platelets. In addition, tyramine and reserpine stimulated the formation of sulfoconjugated noradrenaline. The efflux of noradrenaline from platelets was measured in parallel and was found to be directly related to the proportion of non metabolized to metabolized noradrenaline in the cells. Unlike tyramine, which induced a similar release of noradrenaline and 5-HT, reserpine was less effective at inducing noradrenaline release than 5-HT release. This study indicates a preferential localization of noradrenaline in the granular pool of human platelets with the existence of an extragranular sulfoconjugated pool which is increased when the granular storage of noradrenaline is impaired. Studies of noradrenaline fluxes and metabolism may be useful in the understanding of both acquired and inherited platelet storage pool defects.

scholarly journals Platelet Antiheparin Activity: Storage Site and Release Mechanism

Blood ◽  
1974 ◽  
Vol 44 (2) ◽  
pp. 157-168 ◽  
Author(s):  
Peter N. Walsh ◽  
Giovanna Gagnatelli
Keyword(s):  
Lysosomal Enzymes ◽  
Time Course ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Human Platelets ◽  
Release Mechanism ◽  
Storage Site ◽  
Dense Granules ◽  
Storage Pool ◽  
Platelet Storage

Abstract The platelet storage and release mechanisms for the heparin-neutralizing activity (HNA), adenosine diphosphate (ADP), serotonin, and lysosomal enzymes were investigated in normal human platelets and in platelets with defective storage or release of ADP and serotonin. The time course of release of HNA from normal washed platelets by thrombin and collagen was slower than that of serotonin. Lysosomal enzymes were not released by collagen from normal washed platelets, whereas under the same conditions HNA was released. In four of six patients with storage pool deficiency, the platelets contained normal amounts of HNA but definitely decreased amounts of ADP and serotonin, whereas in the remaining two patients the total contents of ADP, serotonin, and HNA were all definitely lower than normal. In four of six patients with storage pool deficiency, the amounts and per cents of total HNA released by collagen were normal, whereas the amounts and per cents of total ADP released were diminished compared with normal. Platelets from patients with the aspirinlike platelet release defect and from aspirin-treated normal subjects contained normal quantities of ADP, serotonin, and HNA, but HNA and ADP were not released in response to collagen. It is concluded that either HNA is stored in and released from dense granules by mechanisms different from those for ADP and serotonin, or that HNA is stored in and released from granules other than the dense granules, which contain ADP and serotonin and the α-granules, which contain lysosomal enzymes.

Loss of Thrombin-Induced Ca2+ Mobilization in a Subpopulation of Platelets during Storage

1991 ◽  
Vol 66 (03) ◽  
pp. 350-354 ◽  
Author(s):  
Rob Fijnheer ◽  
Christa H E Homburg ◽  
Berend Hooibrink ◽  
Martine N Boomgaard ◽  
Dirk de Korte ◽  
...  
Keyword(s):  
Human Platelets ◽  
Flow Cytometer ◽  
Maximal Concentration ◽  
Gradual Decline ◽  
Platelet Storage ◽  
Functional Defect ◽  
Total Fluorescence ◽  
Induced Changes

SummaryThrombin-induced changes in cytosolic free Ca2+ ([Ca2+]i) were studied in human platelets that had been stored for up to 6 days. Changes in [Ca2+]i were measured with Indo-1-loaded platelets and quantitated with two different methods: (i) measurement of the changes in total fluorescence; (ii) measurement of the [Ca2+]i changes in individual platelets in a flow cytometer, allowing the detection of non-responding platelets. The maximal concentration of [Ca2+]i after stimulation with 0.5 U of thrombin/ml decreased from 544 ± 58 nM (mean ± SEM, n = 6) on day 0, to 276 ± 9 nM on day 3 and to 203 ± 23 nM on day 6. The percentage of platelets responding to 0.5 U of thrombin/ml declined from 90 ± 2% on day 0 to 72 ± 4% on day 3, and to 47 ± 8% on day 6. Nevertheless, also the responding platelets showed a decreased rise in [Ca2+]i.The study shows that during platelet storage a decrease in the rise in [Ca2+]i upon thrombin stimulation occurs. This decrease is partly due to the formation of a subpopulation of platelets that is completely unresponsive and partly due to a decreased responsiveness in the remainder of the platelets; it is not due to a gradual decline in [Ca2+]i rise in all platelets. This phenomenon provides new insight in the functional defect of stored platelets.

Detection of an Acquired Platelet Storage Pool Disease in Three Patients with a Myeloproliferative Disorder

1979 ◽  
Vol 42 (02) ◽  
pp. 794-796 ◽  
Author(s):  
Francine Rendu ◽  
Marilyne Lebret ◽  
Alan Nurden ◽  
Jacques P Caen
Keyword(s):  
Myeloproliferative Disorder ◽  
Storage Pool ◽  
Platelet Storage ◽  
Storage Pool Disease

scholarly journals A Platelet Acquired Storage Pool Disorder Associated with Tamoxifen Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Lalitha Nayak ◽  
Alvin H. Schmaier
Keyword(s):  
Breast Cancer ◽  
Platelet Function ◽  
Tooth Extraction ◽  
Function Analysis ◽  
Tamoxifen Therapy ◽  
Storage Pool ◽  
Prolonged Bleeding ◽  
Platelet Storage

The antiestrogenic drug tamoxifen, used in patients with breast cancer, is associated with an increase in arterial and venous thrombotic events, the mechanism of which is not clearly understood. We report a case of a lady who presented with new bruising and prolonged bleeding following a tooth extraction 4–6 weeks after starting tamoxifen. Investigations were consistent with an acquired platelet storage pool disorder. Repeat platelet function analysis was normal, performed 3 months after discontinuation of tamoxifen. We present a previously clinically unreported effect of tamoxifen on platelet function.

Transfer of arachidonic acid from phosphatidylcholine to phosphatidylethanolamine during storage of human platelets for 5 days

1990 ◽  
Vol 68 (1) ◽  
pp. 117-122 ◽  
Author(s):  
Julie Lacasse ◽  
Rosalind S. Labow ◽  
Morris Kates ◽  
George A. Adams
Keyword(s):  
Arachidonic Acid ◽  
Storage Conditions ◽  
Phospholipid Metabolism ◽  
Human Platelets ◽  
Acyl Transfer ◽  
Acid Uptake ◽  
Molar Composition ◽  
Platelet Storage ◽  
Head Groups ◽  
Glycerol Uptake

Human platelets are routinely stored for 5 days prior to transfusion, but they deteriorate during storage. Since very little information is available concerning the effect of storage on platelet phospholipid metabolism, the biosynthesis and remodelling of platelet phospholipids were studied. Platelets were incubated separately with [14C]glycerol, [14C]arachidonic acid, or a mixture of [14C]glycerol and [3H]arachidonic acid, and stored in a platelet storage medium at 22 °C. Maximum glycerol uptake (20%) was attained after 6 h. [14C]Glycerol was incorporated into phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, and to a much lesser extent phosphatidylserine, under storage conditions for 5 days. The distribution of the initial arachidonic acid uptake was not as would be expected based on the molar composition of endogenous phospholipids. The arachidonic acid (75%) which was taken up within 10 min of incubation distributed 55% into the phosphatidylcholine and only 14% into the phosphatidylethanolamine; the molar composition is actually 18% phosphatidylcholine and 47% phosphatidylethanolamine. During storage, there was a continuous transfer of the radiolabeled arachidonic acid from phosphatidylcholine to phosphatidylethanolamine until, after 5 days, the distribution of arachidonic acid was identical to the endogenous distribution. In contrast, no change in the glycerol incorporation pattern was detected during storage. This suggested that the mechanism for arachidonic acid redistribution was not through exchange of polar head groups, but through acyl transfer of arachidonic acid from phosphatidylcholine to phosphatidylethanolamine.Key words: human, platelet, storage, arachidonate, phospholipids.

scholarly journals Immature dense granules in platelets from mice with platelet storage pool disease

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1300-1306 ◽  
Author(s):  
M Reddington ◽  
EK Novak ◽  
E Hurley ◽  
C Medda ◽  
MP McGarry ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Dense Granule ◽  
Mutant Mice ◽  
Normal Numbers ◽  
Group Of Seven ◽  
Dense Granules ◽  
Storage Pool ◽  
Platelet Storage ◽  
Transmission Electron ◽  
Storage Pool Disease

Mepacrine uptake into platelets and bone marrow megakaryocytes was analyzed to further characterize the dense granule defects in a group of seven mouse pigment mutants that have characteristics of platelet storage pool disease (SPD). In contrast to our previous studies using electron microscopy, this method revealed that all mutants had normal numbers of dense granules. However, total mepacrine uptake in all mutant platelets was significantly diminished to less than 50% of normal uptake. Also, the flashing phenomenon observed when normal dense granules are irradiated with ultraviolet light was either greatly diminished or absent when platelets of individual mutants were similarly irradiated. Therefore the principal defect in the mutant platelets is an inability to accumulate dense granule contents rather than an absence of the granules. Mepacrine uptake into megakaryocytes was indistinguishable in normal and mutant mice. This indicates the mutant dense granule defects appear either very late in megakaryocyte development or early in platelet formation in correlation with development of the mature dense granule. By standard transmission electron microscopy we have not been able to detect gross structural or subcellular abnormalities in either platelets or megakaryocytes of mutant mice. It appears all seven mutants produce immature or functionally abnormal dense granules.

scholarly journals Correction of symptoms of platelet storage pool deficiency in animal models for Chediak-Higashi syndrome and Hermansky-Pudlak syndrome

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1196-1201
Author(s):  
EK Novak ◽  
MP McGarry ◽  
RT Swank
Keyword(s):  
Bone Marrow ◽  
Animal Models ◽  
Dense Granule ◽  
Whole Body ◽  
Inherited Disorders ◽  
Humoral Factors ◽  
Storage Pool ◽  
Platelet Storage ◽  
Hermansky Pudlak Syndrome ◽  
Chediak Higashi Syndrome

Two human diseases of platelet storage pool deficiency (SPD), Hermansky- Pudlak syndrome and Chediak-Higashi syndrome, are recessively inherited disorders characterized by hypopigmentation, prolonged bleeding, and normal platelet counts accompanied by a reduction in dense granule number. We have recently described seven independent recessive mutations in the mouse regulated by separate genes which are likely animal models for human SPD. Reciprocal bone marrow transplants were carried out between normal C57BL/6J mice and two of these mutants, beige and pallid, in order to test whether the platelet defects are due to a defect in platelet progenitor cells or to humoral factors. Normal and congenic mutant mice were transplanted with marrow after 950 rad whole body radiation. The long bleeding times and low serotonin concentrations of the two mutants were converted to normal values after transplantation with normal marrow. Likewise, normal mice displayed symptoms of SPD when transplanted with mutant marrow. These studies demonstrate that with each of the two mutations, platelet SPD results from a defect in bone marrow precursor cells. Also, the studies suggest that in severe cases, platelet SPD may be successfully treated by bone marrow transplantation.

A Functional Basis For The Platelet Storage Pool Deficiency In Chediak-Higashi Cattle

1981 ◽  
Author(s):  
K M Meyers ◽  
M Fukami ◽  
H Holmsen
Keyword(s):  
Freeze Fracture ◽  
Subcellular Fractionation ◽  
Dense Granule ◽  
Bivalent Cation ◽  
Fibrous Matrix ◽  
Dense Granules ◽  
Storage Pool ◽  
Common Basis ◽  
Platelet Storage ◽  
Amine Storage

Platelets from cattle with the morphologic homolog of the Chediak-Higashi (CH) syndrome are essentially devoid of secretable nucleotides and serotonin. There are reduced but still substantial amounts of secretable calcium and magnesium. The storage pool deficiency may be, in part, due to a functional granule defect. Platelets from CH cattle take up serotonin and protect it from degradation for several hours. If these platelets are treated with thrombin, serotonin and bivalent cations are released by mechanisms similar to that of secretion, suggesting a granule location for the released serotonin and cations. This suggestion is verified by subcellular fractionation studies where platelets are first incubated with 14C-serotonin then lysed using a French press. Organelles were then separated on a sucrose gradient by centrifugation. Serotonin in normal bovine platelets is associated with the dense granule or pellet while in CH platelets serotonin is primarily found in a region of the sucrose density zone that in normal platelets contain alpha granules. These findings suggested that some granules in CH platelets are able to acquire the bivalent cation and amine but not the nucleotide component of the bivalent cation-nucleotide-amine storage complex that is thought to occur in normal dense granules.Ultrastructural identification of the serotonin-containing CH granule is not known. There are 2 identifiable granule populations in CH platelets, alpha granules and fibrous matrix granules. Based on serial sectioning freeze fracture and morphometric studies, there are less than 4 of these granules/platelet. Mepacrine studies also demonstrate 2 granule populations. One population has an incidence of 2 per granule and characteristics of normal dense granules. Since the number of fibrous matrix granules and mepacrine granules is similar, a common basis for these granules which has at least some dense granule characteristics, i.e., mepacrine storage, is suggested.

scholarly journals Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors

2020 ◽  
Vol 30 (12) ◽  
pp. 6135-6151 ◽  
Author(s):  
Travis J Bacon ◽  
Anthony E Pickering ◽  
Jack R Mellor
Keyword(s):  
Noradrenaline Release ◽  
Information Transfer ◽  
Pyramidal Neurons ◽  
Schaffer Collateral ◽  
Release Of Noradrenaline ◽  
Ca1 Pyramidal Neurons ◽  
Endogenous Noradrenaline ◽  
Memory Representations ◽  
Endogenous Release ◽  
Ca1 Pyramidal Neuron

Abstract Release of the neuromodulator noradrenaline signals salience during wakefulness, flagging novel or important experiences to reconfigure information processing and memory representations in the hippocampus. Noradrenaline is therefore expected to enhance hippocampal responses to synaptic input; however, noradrenergic agonists have been found to have mixed and sometimes contradictory effects on Schaffer collateral synapses and the resulting CA1 output. Here, we examine the effects of endogenous, optogenetically driven noradrenaline release on synaptic transmission and spike output in mouse hippocampal CA1 pyramidal neurons. We show that endogenous noradrenaline release enhances the probability of CA1 pyramidal neuron spiking without altering feedforward excitatory or inhibitory synaptic inputs in the Schaffer collateral pathway. β-adrenoceptors mediate this enhancement of excitation-spike coupling by reducing the charge required to initiate action potentials, consistent with noradrenergic modulation of voltage-gated potassium channels. Furthermore, we find the likely effective concentration of endogenously released noradrenaline is sub-micromolar. Surprisingly, although comparable concentrations of exogenous noradrenaline cause robust depression of slow afterhyperpolarization currents, endogenous release of noradrenaline does not, indicating that endogenous noradrenaline release is targeted to specific cellular locations. These findings provide a mechanism by which targeted endogenous release of noradrenaline can enhance information transfer in the hippocampus in response to salient events.

scholarly journals Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sanjeev Kiran Gotru ◽  
Johanna P. van Geffen ◽  
Magdolna Nagy ◽  
Elmina Mammadova-Bach ◽  
Julia Eilenberger ◽  
...  
Keyword(s):  
Human Platelets ◽  
Storage Pool
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