Electron microscopical observations on the surface coating of human blood platelets

Behnke, O.

doi:10.1016/s0022-5320(68)80016-4

Cited by 169 publications

(53 citation statements)

References 48 publications

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“…1). This rapid uptake suggested that most of the drug binds directly to the plasma membrane of the platelet or to the layer of plasma protein surrounding this membrane (Nakao & Angrist, 1968;Behnke, 1968 Table 1). Maximal binding of quinidine was 53% when the total quinidine concentration was 10-lm.…”

Section: Resultsmentioning

confidence: 99%

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

Boullin

O'Brien

1971

British J Pharmacology

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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.

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Section: Resultsmentioning

confidence: 99%

“…Plasma proteins form an outer layer on the platelet membrane (Nakao & Angrist, 1968;Behnke, 1968). These molecules might therefore bind considerable amounts of quinidine, and it has been suggested that quinidine acts on cells by virtue of avid binding to membrane proteins, thereby altering cell permeability (Conn & Luchi, 1961).…”

Section: Discussionmentioning

confidence: 99%

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

Boullin

O'Brien

1971

British J Pharmacology

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“…In addition, platelets were found by electron microscopy to be surrounded by an electron-dense "glycocalyx" that is rich in fibrinogen, 14 a plasma protein that was later discovered to enjoy an intimate relationship with ␣IIb␤3 (reviewed in Marcus and Zucker, 13 Peerschke, 15 and Bennett 16 ).…”

Section: Introductionmentioning

confidence: 99%

The GPIIb/IIIa (integrin αIIbβ3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend

Coller

Shattil

2008

Blood

318

342

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Starting 90 years ago with a clinical description by Glanzmann of a bleeding disorder associated with a defect in platelet function, technologic advances helped investigators identify the defect as a mutation(s) in the integrin family receptor, ␣IIb␤3, which has the capacity to bind fibrinogen (and other ligands) and support platelet-platelet interactions (aggregation). The receptor's activation state was found to be under exquisite control, with activators, inhibitors, and elaborate inside-out signaling mechanisms controlling its conformation. Structural biology has produced high-resolution images defining the ligand binding site at the atomic level. Research on ␣IIb␤3 has been bidirectional, with basic insights resulting in improved Glanzmann thrombasthenia carrier detection and prenatal diagnosis, assays to identify single nucleotide polymorphisms responsible for alloimmune neonatal thrombocytopenia, and the development of ␣IIb␤3 antagonists, the first rationally designed antiplatelet agents, to prevent and treat thrombotic cardiovascular disease. The future looks equally bright, with the potential for improved drugs and the application of gene therapy and stem cell biology to address the genetic abnormalities. The ␣IIb␤3 saga serves as a paradigm of rigorous science growing out of careful clinical observations of a rare disorder yielding both important new scientific information and improved diagnosis, therapy, and prevention of other disorders. (Blood. 2008;112: 3011-3025) Introduction"Thus blood, for all its raw physicality, its heat, color and smell, remains first and foremost a powerfully symbolic substancecapable of representing the most primeval forces of life, and of death." 1 "… for the blood is life …" Deuteronomy 12:23To celebrate the 50th anniversary of Blood, we offer an historical account of research on our favorite receptor on the platelet surface, GPIIb/IIIa, or integrin ␣IIb␤3. This receptor plays an important role in hemostasis and thrombosis, and in accord with the quotations above, both processes have profound effects on life and health. The origin of the English word blood is uncertain. It may derive from a postulated Indo-European root bhel, "bloom" or "sprout," and it has been speculated that "ancient people looked upon the effusion from incised skin as a sort of blooming," 2 an image well known to practitioners of the bleeding time.The dominant theme in this review is how improved understanding of the structure and function of ␣IIb␤3 has led to opportunities to translate that knowledge into biomedical advances, including the development of ␣IIb␤3 antagonists, the first class of rationally designed antiplatelet agents. The subtheme is how advances in scientific technology deriving from discoveries in other fields have been crucial to improving our understanding of ␣IIb␤3. Figure 1 is a timeline depicting, by category, approximately when different technologies were introduced into the investigation of blood platelets and/or ␣IIb␤3. Thus, as with a musical fugue, we will try to tell 2 sto...

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“…In a similar manner, trypsin appears to hydrolyse surface located proteins in blood platelets. Behnke (1968) reported that trypsin removed the ruthenium-red stainable material from the surface of both rat and human platelets, but had no effect on the electron dense staining produced by incubation with either colloidal iron or thorotrast. Pepper & Jamieson (1970) found that pretreatment of platelets with trypsin released glycoprotein fragments from the platelet membrane; similar treatment also decreased the sialic acid content of the platelet membranes (Barber & Jamieson, 1971).…”

Section: Adenine Transportmentioning

confidence: 99%

Effect of Selective Proteolysis on the Accumulation of 5‐hydroxytryptamine by Intact Rat Blood Platelets

Sneddon¹,

Williams²

1974

British J Pharmacology

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The effect of perturbation of intact blood platelets with proteolytic enzymes was studied with respect to 5‐hydroxytryptamine (5‐HT) transport, adenine transport and intracellular Na+ and K+ levels. Leucine aminopeptidase and thrombin reduced 5‐HT transport, released 5‐HT from pre‐labelled platelets and disturbed the gradient to monovalent cations. Leucine aminopeptidase, but not thrombin, inhibited adenine transport. α‐Chymotrypsin and carboxypeptidases A and B were without effect on the parameters studied. Trypsin selectively reduced 5‐HT transport. It did not release 5‐HT from blood platelets or inhibit adenine transport. The action of proteolytic enzymes is discussed in terms of proteins localized in the external membrane that may function in part as membrane carriers.

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Electron microscopical observations on the surface coating of human blood platelets

Cited by 169 publications

References 48 publications

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

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

The GPIIb/IIIa (integrin αIIbβ3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend

Effect of Selective Proteolysis on the Accumulation of 5‐hydroxytryptamine by Intact Rat Blood Platelets

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