Forskning ved Københavns Universitet - Københavns Universitet


Toxicodynamics of tumour promoters of mouse skin III. Specific binding of the tumour promoter thapsigargin as measured by the cold-acetone filter assay

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A method is described for measuring rapid, specific, and saturable binding of the skin irritant and tumour-promoting secretagogue thapsigargin (sesquiterpene lactone) to the microsomal fraction from mouse brain. Employing the tritium-labelled compound its apparent dissociation constant, Kd, and the maximal amount of binding Bmax are shown to be 9.8 n M and 1.9 pmol/mg protein respectively. Such a Kd for thapsigargin is similar to (a) its IC50 value for inhibiting Ca2+ uptake in the microsomal fraction from rat brain and (b) its EC50 values for inducing a rise in the cytoplasmic Ca2+ concentration of human platelets and histamine release from rat peritoneal mast cells. A positive correlation is found between the binding affinities of thapsigargin, thapsitranstagin, and trilobolide, their potencies as secretagogues and their lipophilicities. This correlation does not extend to the skin-irritant activities of the compounds thus emphasizing that their mechanism of action is unlike that of 12-O-tetradecanoylphorbol 13-acetate.

TidsskriftJournal of Cancer Research and Clinical Oncology
Udgave nummer5
Sider (fra-til)344-348
Antal sider5
StatusUdgivet - 1 maj 1992

ID: 232598281