Two distinct pathways in the down-regulation of type-1 angiotension II receptor gene in rat glomerular mesangial cells.
The mRNA level of the type-1 angiotensin II receptor (AT1) was down-regulated by angiotensin II in cultured rat glomerular mesangial cells. The effect was maximum with 1 microM AII at 6 h, sensitive to cycloheximide, and specific to AT1 since this phenomenon was blocked by DuP753, an AT1 antagonist, but not by type-2 antagonist PD123319. Dibutyryl cAMP, forskolin, and cholera toxin also caused AT1 down-regulation. These effects were not altered by either the protein kinase A inhibitor H-8 or cycloheximide. Calcium ionophore A23187, pertussis toxin, protein kinase C inhibitor staurosporine, or prolonged incubation with phorbol ester were without effect. These results suggest that there are at least two pathways to down-regulate AT1 mRNA; one way is an angiotensin II-induced, protein kinase C-independent, and cycloheximide-sensitive pathway and the other is an angiotensin II-independent, cAMP-induced, and cycloheximide-insensitive pathway.
Makita
N
N
Division of Nephrology, Vanderbilt University, Nashville, TN 37232.
Iwai
N
N
Inagami
T
T
Badr
K F
KF
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D005920:Glomerular Mesangium / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000235:genetics*; D015398:Signal Transduction
D057911:Angiotensin Receptor Antagonists; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003513:Cycloheximide