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Article Title

Dibutyryl cAMP down-regulates gene expression of endothelin receptor A subtype in rat astrocytoma C6 cells

Abstract

In this study, we have investigated the gene expression of endothelin receptors in rat astrocytoma C6 cells regulated by the increase of intracellular cAMP. Following treatment with 1 mM dibutyryl cAMP, the specific binding of [125I]-endothelin-1 to the C6 cells was down-regulated to about 40 % of the original level. Radioligand binding assay and Northern blot analysis indicated that endothelin receptors on C6 cells, which were either treated or untreated with 1 mM dibutyryl cAMP, belong to subtype A. Analysis of RNA by Northern blotting and slot hybridization demonstrated that the presence of dibutyryl cAMP induced the down regulation of ET(A) endothelin receptor gene in C6 cells. The level of ET(A) mRNA was rapidly reduced to about 10 % of its initial level after 4 hour treatment with dibutyryl cAMP and then was slightly elevated to about 40 % after one day treatment. All the findings suggest that the down regulation of ET(A) receptor in C6 cells by the treatment of dibutyryl cAMP occurs not only at the receptor binding level but also at the mRNA level.

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