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. 1992;118(5):344-8.
doi: 10.1007/BF01294438.

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

S B Christensen  1 , M Hergenhahn, H Roeser, E Hecker
Affiliations

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

S B Christensen et al. J Cancer Res Clin Oncol. 1992.

Abstract

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 nM 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.

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References

    1. Ali H, Christensen SB, Foreman JC, Pearce FL, Piotrowski W, Thastrup O (1985) The ability of thapsigargin and thapsigargicin to activate cells involved in the inflammatory response. Br J Pharmacol 85:705–712 - PMC - PubMed
    1. Ashendel CL, Boutwell RK (1981) Direct measurement of specific binding of highly lipophilic phorbol diester to mouse epidermal membranes using cold acetone. Biochem Bophys Res Commun 99:543–549 - PubMed
    1. Bennett JP (1978) Methods in binding studies in neurotransmitter receptor binding. In: Yamamura HI, Enna SJ, Kuhar MJ (eds) Neurotransmitter receptor binding. Raven Press, New York, pp 57–90
    1. Christensen SB (1985) Radiolabelling of the histamine liberating sesquiterpene lactone, thapsigargin. J Labelled Compd Radiopharm 22:71–77
    1. Christensen SB, Andersen A, Lauridsen A, Moldt P, Smitt U, Thastrup O (1992) Thapsigargin a lead to design of drugs with the calcium pump as target. In: Krogsgaard-Larsen P, Christensen SB, Kofod H (eds) New lead and targets in drug design. Munksgaard, Copenhagen (in press)

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