The beta-adrenoceptor-coupled adenylate cyclase system in rat C6 glioma cells. Deamplification by isoproterenol and oxaprotiline.
The beta-adrenoceptor-coupled adenylate cyclase system in rat C6 glioma cells displays many characteristics observed in brain tissue: using nonlinear regression analysis of agonist competition binding curves, we demonstrated that the bulk of beta-adrenoceptors show high nanomolar affinity for isoproterenol; like in brain tissue, Gpp(NH)p does not shift agonist competition binding curves to the right; and the agonist isoproterenol rapidly downregulates the number of beta-adrenoceptors and deamplifies the norepinephrine signal. However, unlike in brain tissue, where (-)-oxaprotiline fails to decrease the number of beta-adrenoceptors and to desensitize the cyclic adenosine monophosphate generating system, it desensitizes the beta-adrenoceptor-coupled adenylate cyclase system in C6 glioma cells. Determination of the relative steady-state levels of beta-adrenoceptor messenger ribonucleic acid (mRNA) by Northern blot analysis showed a twofold increase in the steady-state levels of the mRNA at 30 minutes following exposure to (-)-isoproterenol or (-)-oxaprotiline. At 48 hours, basal values of mRNA were observed at a time when beta-adrenoceptors were maximally decreased. Further experiments on transcriptional activation, and mRNA stability and translation will be required to unravel the complexity of agonist-dependent and agonist-independent regulation of beta-adrenoceptor density and function.
Manier
D H
DH
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Bieck
P R
PR
Duhl
D M
DM
Gillespie
D D
DD
Sulser
F
F
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001345:Autoradiography; D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000201:enzymology*; D002478:Cells, Cultured; D015342:DNA Probes; D005910:Glioma / Q000201:enzymology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008376:Maprotiline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012044:Regression Analysis; D014407:Tumor Cells, Cultured
D000928:Antidepressive Agents; D015342:DNA Probes; D011943:Receptors, Adrenergic, beta; D008376:Maprotiline; D006165:Guanylyl Imidodiphosphate; C027299:hydroxymaprotilin; D012313:RNA; D000262:Adenylyl Cyclases; D007545:Isoproterenol