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Related Experiment Videos

Colchicine uptake and binding by human platelets

D M Kenney, F C Chao, J L Tullis

    Thrombosis Et Diathesis Haemorrhagica
    |December 15, 1975
    PubMed
    Summary
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    Human platelets bind the antimitotic drug colchicine. Thrombin and cold exposure increase this binding by affecting platelet microtubules, suggesting new binding sites may become available.

    Area of Science:

    • Biochemistry
    • Cell Biology
    • Pharmacology

    Background:

    • Colchicine is an antimitotic alkaloid.
    • Platelets play crucial roles in hemostasis and thrombosis.
    • Understanding drug interactions with cellular components is vital.

    Purpose of the Study:

    • To investigate the uptake and binding of colchicine in human platelets.
    • To explore the factors influencing colchicine binding, including temperature, ions, and thrombin.
    • To elucidate the relationship between colchicine binding and platelet microtubule dynamics.

    Main Methods:

    • Utilized a silicone oil centrifugation technique to separate platelets.
    • Employed radiolabeled 14C-colchicine to quantify uptake and binding.
    • Examined the effects of temperature, magnesium, GTP, calcium, cold, and thrombin on colchicine binding.

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    Main Results:

    • Colchicine uptake and binding in platelets are reproducible, time-dependent, and specific.
    • Binding is temperature-dependent, with increased uptake/binding observed at 4°C or upon thrombin exposure.
    • Magnesium and GTP enhance binding in lysed platelets, while calcium inhibits it.

    Conclusions:

    • Thrombin and cold disrupt platelet microtubules, leading to increased colchicine binding.
    • These findings suggest thrombin may facilitate the availability of colchicine binding sites (microtubule subunits) within platelets.
    • Colchicine binding is a sensitive indicator of changes in platelet microtubule structure.