Open AccessDrugs that Influence Tubulin Polymerization Modulate Thyrotropin‐Releasing Hormone Receptor Number in AtT‐20 Cells
Author(s) -
Ravindra R.,
McIlroy P. J.,
Patel S. A.
Publication year - 1997
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1111/j.1600-0773.1997.tb00279.x
Subject(s) - colchicine , receptor , vinblastine , tubulin , thyrotropin releasing hormone , biology , hormone receptor , microbiology and biotechnology , cell , cell culture , hormone , microtubule , chemistry , medicine , endocrinology , biochemistry , genetics , chemotherapy , cancer , breast cancer
In order to examine the role of cytoskeleton in modulating the cell surface receptors, AtT‐20 cells (stably expressing thyrotropin‐releasing hormone receptors) were incubated with drugs that are known to modify the tubulin‐microtubule system. The binding of [ 3 H]methyl thyrotropin‐releasing hormone ([ 3 H]mTRH) to intact cells increased as a function of time, and was linear from 1.25x10 6 to 6.25x10 6 cells/ml. Cells incubated with colchicine, vinblastine, and taxol for 16 hr were harvested and the cell concentration was determined using a haemocytometer. Because the drugs inhibited the cell proliferation at 100 nM, it was decided to examine the effect of 100 nM of each of the three drugs on the ability of [ 3 H]mTRH to bind cell surface receptors. Cells were incubated with the drugs for 16 hr at 37°. After the incubation, cells (5x10 6 cells/ml) from each group were assayed for [ 3 H]mTRH binding. Colchicine, vinblastine, and taxol stimulated [ 3 H]mTRH binding by up to 27, 27, and 21%, respectively, without altering the K a of the ligand to the receptor. These results suggest that perturbation of cytosolic microtubules leads to a reorganization of the spatial location of hormone receptors.