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Functional interaction between angiotensin ii and grk5 in cultured vascular smooth muscle cells (vsmc) and rat aorta

Publication ,  Journal Article
Ishizaka, N; Griendling, K; Fukui, T; Oppermann, M; Lefkowitz, R; Alexander, R
Published in: FASEB Journal
December 1, 1996

G protein receptor kinases (GRKs) are involved in receptor desensitization. In HEK293 cells overexpressing the angiotensin II (ang U) ATiA receptor (ATjAR) and GRK5, the ATjAR is a substrate for GRK5 and coupling to phospholipase C (PLC) is diminished. In the current study, we examined the interaction between ang II and GRKS in cultured VSMC from rat aorta, both in terms of functional consequences and long-term regulation. We stably transfected VSMC with a 1.8 kb fragment of bovine antisense GRK5, and measured GRK5 mRNA and protein expression, as well as ang n activation of PLC and phospholipase D (PLD). In antisense transfected cells, GRK5 mRNA was reduced by 64%. Both PLC and PLD activity, as measured by [3H]inositol and [3H]choline release, were increased (129±19% and 144±14% nontransfected levels, respectively), suggesting that GRK5 may be involved in the normal termination of VSMC ATi A& signaling. We next examined ang II regulation of GRKS expression. In cultured VSMC, GRK5 mRNA and protein is upregulated by exposure to 100 nM ang n for 16 h (453±27%). In aortas from rats receiving continuous infusion of ang II (0.7mg/ kg/day), GRK5 is also upregulated after 5 days (303±20%). This upregulation is completely blocked by the ATiAR antagonist losartan, and partially by the nonspecific vasodilator hydralazine, implying that GRKS may be regulated both by ang II and elevated blood pressure. In conclusion, GRKS appears to modulate AT| AR signaling in VSMC, and is itself regulated by ang II, suggesting a novel mechanism for regulating VSMC sensitivity to ang H.

Duke Scholars

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

December 1, 1996

Volume

10

Issue

6

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

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Ishizaka, N., Griendling, K., Fukui, T., Oppermann, M., Lefkowitz, R., & Alexander, R. (1996). Functional interaction between angiotensin ii and grk5 in cultured vascular smooth muscle cells (vsmc) and rat aorta. FASEB Journal, 10(6).
Ishizaka, N., K. Griendling, T. Fukui, M. Oppermann, R. Lefkowitz, and R. Alexander. “Functional interaction between angiotensin ii and grk5 in cultured vascular smooth muscle cells (vsmc) and rat aorta.” FASEB Journal 10, no. 6 (December 1, 1996).
Ishizaka N, Griendling K, Fukui T, Oppermann M, Lefkowitz R, Alexander R. Functional interaction between angiotensin ii and grk5 in cultured vascular smooth muscle cells (vsmc) and rat aorta. FASEB Journal. 1996 Dec 1;10(6).
Ishizaka N, Griendling K, Fukui T, Oppermann M, Lefkowitz R, Alexander R. Functional interaction between angiotensin ii and grk5 in cultured vascular smooth muscle cells (vsmc) and rat aorta. FASEB Journal. 1996 Dec 1;10(6).

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

December 1, 1996

Volume

10

Issue

6

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology