A beta-adrenergic agonist modulates DR alpha gene transcription via enhanced cAMP levels in a glioblastoma multiforme line.
In this study we have examined the ability of the beta-adrenergic agonist isoproterenol (ISO) to alter the expression of the human MHC class II Ag, DR, on a glioblastoma multiforme cell line. We have determined that ISO induces an increase in both DR alpha-specific RNA and protein. This induction is most likely due to the increase in cAMP levels elicited by the agonist, based on the direct measurements of cAMP levels and the ability of DBcAMP and the adenylate cyclase activator, forskolin to mimic the effects of isoproterenol. Blocking of the induction was achieved with the beta-antagonist, propranolol, but not with the alpha-antagonist phentolamine, indicating that this is a beta-adrenergic receptor-mediated phenomenon. Finally this induction is transcriptionally regulated as determined by nuclear run-on experiments. Future studies will center on identifying DNA regions of the DR alpha-chain gene which are important in this regulation.
Basta
P V
PV
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599-7295.
Moore
T L
TL
Yokota
S
S
Ting
J P
JP
D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D005909:Glioblastoma / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D006684:HLA-DR Antigens; D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D012313:RNA; D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol