Journal article
Bradykinin and angiotensin II: activation of protein kinase C in arterial smooth muscle
American Journal of Physiology: Cell Physiology, Vol.266(5), pp.C1406-C1420
05/01/1994
DOI: 10.1152/ajpcell.1994.266.5.C1406
PMID: 8203504
Abstract
The effects of bradykinin (BK) and angiotensin II (ANG II) were compared in cultured rat mesenteric arterial smooth muscle cells. BK and ANG II activated a phosphoinositide-specific phospholipase C, leading to the rapid release of [3H]inositol phosphates, an increase in intracellular calcium, and formation of sn-1,2-diacylglycerol (DAG). DAG formation was biphasic with a transient peak at 5 s followed by a sustained increase from 60 to 600 s. The BK-mediated increases in inositol triphosphate and DAG were dose dependent with half-maximal increases at concentrations of 5 and 2 nM, respectively. Both hormones were found to activate protein kinase C (PKC) as assessed by phosphorylation of the 68- to 72-kDa intracellular PKC substrate myristoylated alanine-rich C kinase substrate. However, despite similar phosphorylation of this substrate, only ANG II produced a significant increase in membrane-bound PKC activity. The mechanism accounting for the inability of BK to increase membrane-bound PKC activity is unclear. Our studies excluded differential translocation of PKC to the nuclear membrane, production of an inhibitor of membrane-bound PKC activity, and expression of BK and ANG II receptors on different cells as the mechanism. Vascular smooth muscle cells were found to express at least four different PKC isozymes: alpha, delta, zeta, and a faint band for epsilon. All of the isozymes except zeta-PKC were translocated by treatment with the phorbol ester 4 beta-phorbol 12-myristate 13-acetate. However, neither ANG II nor BK produced significant translocation of any measured isozyme; therefore, we could not exclude the possibility that ANG II and BK activate different isozymes of PKC. Both hormones were found to have a similar small and inconsistent effect in stimulating [3H]thymidine incorporation. These observations demonstrate that BK and ANG II have similar biochemical effects on vascular smooth muscle cells and imply that, in selected vessels, the vasodilatory effects of BK mediated by the endothelium may be partially counterbalanced by a vasoconstrictor effect on the underlying vascular smooth muscle cells.
Details
- Title: Subtitle
- Bradykinin and angiotensin II: activation of protein kinase C in arterial smooth muscle
- Creators
- Bradley S Dixon - Department of Medicine, University of Iowa College of Medicine, IowaCityRam V Sharma - Department of Medicine, University of Iowa College of Medicine, IowaCityTy Dickerson - Department of Medicine, University of Iowa College of Medicine, IowaCityJohn Fortune - Department of Medicine, University of Iowa College of Medicine, IowaCity
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.266(5), pp.C1406-C1420
- DOI
- 10.1152/ajpcell.1994.266.5.C1406
- PMID
- 8203504
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Language
- English
- Date published
- 05/01/1994
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094492902771
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