Modulation of alpha1B-adrenoceptor expression by agonist and protein kinase inhibitors.
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.
Bird
K S
KS
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Anderson
J L
JL
Toews
M L
ML
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D019833:Genistein; D011493:Protein Kinase C; D019311:Staurosporine; D004837:Epinephrine