The Relationship Between 5‐hydroxytryptamine and Adenosine Triphosphate in Blood Platelets

Born, G. V. R.; Ingram, G. I. C.; Stacey, R. S.

doi:10.1111/j.1476-5381.1958.tb00191.x

Cited by 47 publications

(28 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We found a decreased content of platelet 5-HT in all seven patients with storage pool disease studied, and the levels showed a good correlation with those obtained for ATP. The latter finding is consistent with previous suggestions that 5-HT and ATP in platelets are complexed, withbivalent cations, as high molecular-weight aggregates (18,48,49). In contrast to the striking decrease in ADP obtained in all patients, the extent to which 5-HT and ATP were decreased was more variable (Fig.…”

Section: Discussionsupporting

confidence: 79%

Studies of Platelet 5-Hydroxytryptamine (Serotonin) in Storage Pool Disease and Albinism

Weiss¹,

Tschopp²,

Rogers³

et al. 1974

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Platelets in patients with storage pool disease are markedly deficient in a nonmetabolic (storage) pool of ADP that is important in platelet aggregation. They are also deficient in ATP, although to a lesser degree. In seven patients with this disorder, including one with albinism, platelet 5-hydroxytryptamine (5-HT) levels were reduced in proportion to the reduction in ATP (r = 0.94). Their platelets show diminished capacity to absorb ["C] 5-HT, and the type of defect was similar to that produced in normal platelets by reserpine, a drug known to inhibit the uptake of 5-HT by the platelet dense granules. Storage pool-deficient platelets also converted more [8H] 5-HT to [3H] 5-hydroxyindoleacetic acid than did normal platelets, and the platelets in one of two patients studied contained increased amounts of 5-HT metabolites. The above findings, together with those reported previously, support the conclusion that the capacity of the dense granules (which may be either diminished or functionally abnormal) for storing 5-HT is decreased in storage pool disease; as a result, the 5-HT that enters the platelet may be more exposed to monoamine oxidases present on mitochondrial membranes. This diminished storage capacity (for 5-HT) may also explain why preincubating platelet-rich plasma with 5-HT for 45 min without stirring inhibits subsequent platelet aggregation by 5-HT to a greater degree in patients with storage pool disease than in normal subjects. The latter finding is also consistent with the theory that the aggregation of platelets by 5-HT is mediated by the same receptors on the plasma membrane that are involved in its uptake. The diminished release of platelet-bound ["C]5-HT by collagen that we found in these patients, as well as findings in previous studies, suggests that the release reaction may also be abnormal in storage pool disease.

show abstract

Section: Discussionsupporting

confidence: 79%

Studies of Platelet 5-Hydroxytryptamine (Serotonin) in Storage Pool Disease and Albinism

Weiss¹,

Tschopp²,

Rogers³

et al. 1974

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Additional experiments in which we measured the change in the total 5-HT (endogenous + 14C-5-HT) and ATP caused by quinidine from 14C-5-HT loaded platelets are summarized in Table 3. The molar ratio of ATP to 5-HT of 2-38 to 1 in these loaded cells is between the value of 1P79 to 1 found by Boullin & O'Brien (1970) in children, and 3'23 to 1 found by Born, Ingram & Stacey (1958) for adults. The quantity of 5-HT released represented 61-4% endogenous and 57% exogenous amine, there being no change in the ratio of exogenous to endogenous indolealkylamine.…”

Section: Effects Of Quinidine On S-ht and Atpmentioning

confidence: 91%

Accumulation of quinidine by human blood platelets: effects on platelet ultrastructure and 5‐hydroxytryptamine

Boullin

O'Brien

1971

British J Pharmacology

View full text Add to dashboard Cite

Summary1. We have studied the mechanism of quinidine uptake by normal human blood platelets. 2. Platelets in plasma or Krebs solution took up quinidine extremely rapidly, the maximal drug concentration ratio of platelet to medium being 24 to 1 after 1 minute. 3. The effects of metabolic inhibitors on uptake were equivocal. Ouabain had no effect but iodoacetate and dinitrophenol were effective. However, as accumulation was not inhibited by low temperature, it was probably not energy dependent. 4. Interactions between quinidine and 5-HT were also investigated. 5. Quinidine blocked 5-HT uptake, but conversely, neither 5-HT itself nor 5-HT uptake inhibitors, such as cocaine, dexamphetamine, and desipramine interfered with quinidine accumulation. 6. Electronmicrographs of platelets incubated with 10-5, 10-4 or 2 x 10-3M quinidine in Krebs solution for 2 h showed no changes at the lower concentrations, but gross ultastructural damage, including disintegration of the plasma membrane, at 2 x 10-3M.7. Further evidence for intracellular penetration was obtained because quinidine released endogenous 5-HT and ATP, and also 14C-5-HT from loaded cells. 8. We conclude that quinidine is taken up by the platelet by a passive process, unrelated to the 5-HT transport mechanism. It is probably accumulated largely in the plasma membrane and outer protein layer, but intracellular penetration and ultrastructural damage may occur.9. Although the effects on 5-HT and ATP were not due to platelet damage, this may occur in vivo and be the cause of quinidine induced thrombocytopenic purpura.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

The Relationship Between 5‐hydroxytryptamine and Adenosine Triphosphate in Blood Platelets

Cited by 47 publications

References 5 publications

Studies of Platelet 5-Hydroxytryptamine (Serotonin) in Storage Pool Disease and Albinism

Studies of Platelet 5-Hydroxytryptamine (Serotonin) in Storage Pool Disease and Albinism

Accumulation of quinidine by human blood platelets: effects on platelet ultrastructure and 5‐hydroxytryptamine

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

Contact Info

Product

Resources

About