Signaling events activated by angiotensin II receptors

What goes before and after the calcium signals

Tamas Balla, P. Várnai, Ying Tian, Roger D. Smith

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Angiotensin II (Ang II) receptors of the AT1 subtype are coupled to heterotrimeric G nucleotide-binding proteins, G(q/11), to activate phospholipase C-β isoforms with production of inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol. The resultant release of intracellular Ca2+ and increased Ca2+ influx are major determinants of several acute cellular responses initiated by Ang II, including secretion of aldosterone from the adrenal cortex and smooth muscle contraction. However, cellular events related to more prolonged effects of Ang II, such as hypertrophic and hyperplastic responses, are triggered by intracellular signaling cascades that are less dependent on Ca2+ signals. The Ang II-induced activation of Raf-1 kinase, p42 MAP-kinase and c-fos expression in response to Ang II in adrenal glomerulosa cells does not require Ca2+ influx. Moreover, the dose- response relationships for Raf-1 activation, MAP-kinase activation and mitogenesis show significantly higher sensitivity to Ang II than the InsP3, Ca2+-release and aldosterone secretory responses. The sensitivities of both Raf-1 kinase and MAP-kinase stimulation by Ang II to the inhibitors of phosphoinositide kinases, wortmannin and LY 294002, suggest that inositol phospholipids may play a role in these activation events unrelated to their role in Ca2+ signaling. To investigate the changes of various inositides after stimulation at the single cell level, fluorescent probes were developed in which pleckstrin homology domains with distinct binding specificities to inositol phospholipids were fused to the green fluorescent protein and expressed in NIH 3T3 cells. The use of these probes revealed heterogeneity of the inositol lipid pools and their complex relationship to Ca2+ signals. The use of these tools will help to further clarify the complex role of these lipids in initiating Ca2+-dependent and -independent signaling responses.

Original languageEnglish
Pages (from-to)335-344
Number of pages10
JournalEndocrine Research
Volume24
Issue number3-4
Publication statusPublished - 1998

Fingerprint

Angiotensin Receptors
Angiotensin II
Proto-Oncogene Proteins c-raf
Calcium
Mitogen-Activated Protein Kinase Kinases
Phosphatidylinositols
Aldosterone
Zona Glomerulosa
Lipids
NIH 3T3 Cells
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Inositol 1,4,5-Trisphosphate
1-Phosphatidylinositol 4-Kinase
Adrenal Cortex
Mitogen-Activated Protein Kinase 1
Diglycerides
Type C Phospholipases
Inositol
Muscle Contraction
Green Fluorescent Proteins

ASJC Scopus subject areas

  • Endocrinology

Cite this

Signaling events activated by angiotensin II receptors : What goes before and after the calcium signals. / Balla, Tamas; Várnai, P.; Tian, Ying; Smith, Roger D.

In: Endocrine Research, Vol. 24, No. 3-4, 1998, p. 335-344.

Research output: Contribution to journalArticle

Balla, Tamas ; Várnai, P. ; Tian, Ying ; Smith, Roger D. / Signaling events activated by angiotensin II receptors : What goes before and after the calcium signals. In: Endocrine Research. 1998 ; Vol. 24, No. 3-4. pp. 335-344.
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