Two distinct pathways in the down-regulation of type-1 angiotensin II receptor gene in rat glomerular mesangial cells

Naomasa Makita, Naoharu Iwai, Tadashi Inagami, Kamal F. Badr

Research output: Contribution to journalArticlepeer-review

Abstract

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 μM 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.

Original languageEnglish (US)
Pages (from-to)142-146
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume185
Issue number1
DOIs
StatePublished - May 29 1992
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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