Modulation of alpha1B-adrenoceptor expression by agonist and protein kinase inhibitors

European Journal of Pharmacology
K S BirdMyron L Toews

Abstract

The agonist-induced up-regulation of alpha1B-adrenoceptors in clone H99 of transfected Chinese hamster ovary cells that we reported previously (Zhu et al., 1996) was further investigated. Studies with a larger number of clones revealed that the up-regulation observed in H99 cells is atypical and that most other clones exhibit down-regulation under the same conditions. The role of protein kinases in the up-regulation of alpha1B-adrenoceptors in clone H99 was further investigated. Surprisingly, the protein kinase inhibitor staurosporine induced a similar up-regulation. Neither the selective protein kinase C inhibitor GF109203X nor the activator phorbol 12-myristate, 13-acetate altered receptor expression. The tyrosine kinase inhibitors genistein and its weaker analog daidzein did not induce up-regulation but blocked the up-regulation induced by epinephrine and by staurosporine. Up-regulation was blocked by the protein synthesis inhibitor cycloheximide. These studies suggest multiple mechanisms by which different protein kinases can modulate the expression of transfected alpha1B-adrenoceptors.

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Citations

Dec 5, 2006·Biochemical Pharmacology·Peter Hein, Martin C Michel

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