Accumulation of dopamine by blood platelets from normal subjects and parkinsonian patients under treatment with L-DOPA.
TL;DR: 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 inbrain neurones in Parkinson's disease.
Abstract: 1. Human blood platelets have been shown to take up dopamine by an energy-dependent, 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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TL;DR: Experimental evidence is reviewed, which uses the human platelet model to investigate neurotransmitter-related abnormalities in Down syndrome, mental retardation, infantile autism, hyperactivity syndromes, schizophrenia, affective disorders, Duchenne muscular dystrophy, Parkinson disease, Huntington chorea, and migraine headaches.
Abstract: • Comparison of the properties of blood platelets and serotonergic synaptosomes suggests that the human platelet can serve as an appropriate model for the transport, metabolism, and release of serotonin (5-HT) by CNS serotonergic neurons. The study of blood 5-HT levels and platelet 5-HT pharmacodynamics in patients with a variety of psychiatric and neurologic disorders has generated interesting leads into possible abnormalities of CNS 5-HT neurons in these patients. This article reviews the experimental evidence, which uses the human platelet model to investigate neurotransmitter-related abnormalities in Down syndrome, mental retardation, infantile autism, hyperactivity syndromes (minimal brain dysfunction), schizophrenia, affective disorders, Duchenne muscular dystrophy, Parkinson disease, Huntington chorea, and migraine headaches.
385 citations
TL;DR: The present data show that both human and animal platelets contain Ad, NA and dopamine, and the bulk of the CA seems to be stored as unconjugated amines together with 5‐HT, histamine and p‐octopamine in a multitransmitter storage site, namely the5‐HT organelle.
Abstract: 1 The content of adrenaline (Ad), noradrenaline (NA) and dopamine was measured in human, guinea-pig, cat, rabbit and rat blood platelets by a highly sensitive and specific radioenzymatic method.2 In all platelet specimens analyzed, the content of the three catecholamines (CA) was several thousand times lower than that of 5-hydroxytryptamine (5-HT).3 In basal conditions, the NA concentration in platelets and plasma always exceeded that of Ad and dopamine.4 In rat and rabbit platelets, Ad, NA and dopamine were present only in the free (unconjugated) form.5 Platelets of rats with storage pool deficiency (Fawn-hooded) contained much less 5-HT and CA than normal rat platelets.6 Following restraint stress, platelets of Fawn-hooded rats, in contrast to normal rat platelets, did not accumulate CA in spite of a dramatic rise in plasma CA.7 Reserpine, a monoamine depletor, released CA as well as 5-HT from rabbit platelets in vivo.8 Subcellular fractionation experiments with rabbit platelets indicate that both CA and 5-HT are most concentrated in the fraction consisting of pure 5-HT organelles.9 Both in humans and rabbits the concentration gradient between platelets and plasma was much lower for CA than for 5-HT, indicating that a high affinity transport mechanism operates in vivo for 5-HT but not for CA.10 In conclusion, the present data show that both human and animal platelets contain Ad, NA and dopamine. The bulk of the CA seems to be stored as unconjugated amines together with 5-HT, histamine and p-octopamine in a multitransmitter storage site, namely the 5-HT organelle.
153 citations
01 Jan 1985
122 citations
TL;DR: The fact that parkinsonian platelets exhibit impaired dopamine uptake, while age-matched control platelets do not, constitutes the first direct evidence in favor of a generalized dopamine defect in Parkinson's disease.
Abstract: Thirty-five parkinsonian patients (five untreated, six with levodopa only, seven with levodopa plus Ro 4-4602, nine with anticholinergic and/or antihistaminic medication, and eight with the anticholinergic/antihistaminic medication plus amantadine) and 35 age-matched control subjects were studied. Platelets isolated from each individual plasma were incubated with 14C-dopamine. Uptake was found to be decreased to a significant degree in all treated or untreated parkinsonian patients when compared with control subjects. Anticholinergic and/or antihistaminic medication, with or without amantadine, further decreased the dopamine uptake into platelets, while levodopa alone or with Ro 4-4602 returned uptake values to near normal. Dopamine efflux paralleled exactly the uptake values. The fact that parkinsonian platelets exhibit impaired dopamine uptake, while age-matched control platelets do not, constitutes the first direct evidence in favor of a generalized dopamine defect in Parkinson's disease.
117 citations
References
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Journal Article•
TL;DR: With this method serotonin has been shown to be a normal constituent of brain and may be applied to the measurement of serotonin in other tissues.
Abstract: 1. A fluorometric method for the determination of serotonin (5-hydroxytryp-tamine) in brain is described. The procedure involves the use of a spectrophoto-fluorometer which can activate and measure emitted fluorescence continuously from 250 to 650 mµ. Serotonin is activated maximally at 295 mµ and emits fluorescent light which shows a maximum at 550 mµ.
2. With this method serotonin has been shown to be a normal constituent of brain.
3. The fluorescent procedure may be applied to the measurement of serotonin in other tissues.
846 citations
235 citations
"Accumulation of dopamine by blood p..." refers background or result in this paper
...In their experiments on dopamine upake by subcellular storage organelles from rabbit platelets, Da Prada & Pletscher (1969) found that dopamine accumulation was 68% of 5-HT uptake. Our results with normal human platelets show that the two amines were accumulated equally (Fig. 3). In view of this similarity it was surprising that the retention patterns were not similar. Although Bemeis, Pletscher & Da Prada (1969) and Berneis, Da Prada & Pletscher (1969) have shown that both dopamine and 5-HT form micelles with ATP, the present work and Da Prada & Pletscher's experiments referred to above suggest that dopamine has less affinity for ATP than has 5-HT....
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...In their experiments on dopamine upake by subcellular storage organelles from rabbit platelets, Da Prada & Pletscher (1969) found that dopamine accumulation was 68% of 5-HT uptake....
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...Recently Da Prada & Pletscher (1969) have demonstrated the uptake of dopamine by the subcellular 5-HT storage organelles isolated from rabbit platelets....
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TL;DR: A simple device for “dark” injection of firefly lantern extract into solutions is described, and the intensity of the initial light flash of the luciferin-luciferase reaction was found to be proportional to the concentration of ATP and of ADP, after conversion to ATP with the pyruvate-kinase system.
188 citations
TL;DR: The work reported here, a preliminary account of part of which has already appeared, was carried out in order to establish a reliable method for estimating HT in blood, to determinine standards for normal human subjects and to develop a method for evaluating the ability of platelets to absorb HT.
Abstract: It has been shown by Humphrey & Jaques (1954) and by Udenfriend & Weissbach (1954) that 5-hydroxytryptamine (HT) in the blood is carried almost entirely by platelets. This suggested that light might be thrown on the physiological function of HT by an inquiry into its concentration and distribution in blood disorders, especially those in which platelet formation and function are abnormal. Some preliminary work showed that there is, in fact, a very marked reduction in both the whole blood and platelet content of this substance in certain diseases. The work reported here, a preliminary account of part of which has already appeared (Hardisty & Stacey, 1955), was carried out in order to establish a reliable method for estimating HT in blood, to determinine standards for normal human subjects and to develop a method for evaluating the ability of platelets to absorb HT.
166 citations
TL;DR: The antagonism of tryptamine was found to be competitive, and the possible site of its action is discussed, as well as a number of other substances on the uptake of 5-hydroxytryptamine by platelets.
Abstract: Human blood platelets were incubated with 5-hydroxytryptamine and with tryptamine and the uptake of each amine measured. The uptake of tryptamine, unlike that of 5-hydroxytryptamine, was linearly related to the concentration of the amine in the surrounding fluid, was similar in amount at 0° and 37° C and varied directly with the pH of the solution. When both amines were present together the uptake of 5-hydroxytryptamine was depressed. The antagonism of tryptamine was found to be competitive, and the possible site of its action is discussed. The effect of a number of other substances on the uptake of 5-hydroxytryptamine by platelets was examined; of these imipramine, cocaine and chlorpromazine were more potent and dihydroergotamine and lysergic acid diethylamide somewhat less potent than tryptamine in inhibiting uptake.
128 citations