Cross talk between angiotensin AT1 and α1-adrenergic receptors: Angiotensin II downregulates α(1a)-adrenergic receptor subtype mRNA and density in neonatal rat cardiac myocytes

Hong Tai Li, Carlin S. Long, Mary O. Gray, D. Gregg Rokosh, Norman Y. Honbo, Joel S. Karliner

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Signaling mediated by the angiotensin (Ang) II and α1-adrenergic receptor (α1-AR) pathways is important for cardiovascular homeostasis. However, it is unknown whether Ang II has any direct effect on α1-AR expression and signaling in cardiac myocytes. In the present study, we determined α1-AR subtype mRNA levels by RNase protection; receptor density by competition binding with 5-methylurapidil; and α1-AR-mediated c-fos expression by Northern blot analysis. We found that Ang II had no effect on α(1b)- and α(1a)-AR mRNA levels but decreased the α(1a)-AR mRNA level in a time- and dose-dependent manner. The maximal effect occurred at 6 hours with 100 nmol/L Ang II (40.0±8.2% reduction, n=4, P<.01). The decrease in α(1a)- AR mRNA level induced by Ang II is mediated by the Ang II AT1 receptor subtype and is associated with decreased stability of α(1a)-AR mRNA. Corresponding to the changes in the α(1a)-AR mRNA level, Ang II (100 nmol/L, 24 hours) reduced the density of high-affinity sites for 5-methylurapidil (α(1A)-AR) by 29% (56.5±6.4 versus 79.0±11.6 fmol/mg protein, n=4, P<.05). α1-AR-stimulated c-fos induction, which could be blocked by 5- methylurapidil but not by chloroethylclonidine, was attenuated by Ang II preincubation (100 nmol/L, 24 hours). We conclude that there is previously undescribed cross talk between AT1 receptors and α1-ARs. Ang II selectively downregulates α(1a)-AR subtype mRNA and its corresponding receptor as well as α(1a)-AR-mediated expression of the immediate-early gene c-fos in cardiac myocytes.

Original languageEnglish
Pages (from-to)396-403
Number of pages8
JournalCirculation research
Volume81
Issue number3
DOIs
StatePublished - 1997

Keywords

  • Angiotensin II
  • Cardiac myocyte
  • Immediate-early gene
  • α-adrenergic receptor

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