Signaling events activated by angiotensin II receptors: What goes before and after the calcium signals

Citation
T. Balla et al., Signaling events activated by angiotensin II receptors: What goes before and after the calcium signals, ENDOCRINE R, 24(3-4), 1998, pp. 335-344
Citations number
11
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
ENDOCRINE RESEARCH
ISSN journal
0743-5800 → ACNP
Volume
24
Issue
3-4
Year of publication
1998
Pages
335 - 344
Database
ISI
SICI code
0743-5800(1998)24:3-4<335:SEABAI>2.0.ZU;2-Z
Abstract
Angiotensin II (Ang II) receptors of the AT(1) subtype are coupled to heter otrimeric G nucleotide-binding proteins, G(q/11), to activate phospholipase C-P isoforms with production of inositol 1,4,5-trisphosphate (InsP(3)) and diacylglycerol. The resultant release of intracellular Ca2+ and increased Ca2+ influx are major determinants of several acute cellular responses init iated by Ang II, including secretion of aldosterone from the adrenal cortex and smooth muscle contraction. However, cellular events related to more pr olonged 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-kin ase and c-fos expression in response to Ang II in adrenal glomerulosa cells does not require Ca2+ influx. Moreover, the dose-response relationships fo r Raf-1 activation, MAP-kinase activation and mitogenesis show significantl y higher sensitivity to Ang II than the InsP(3), Ca2+-release and aldostero ne secretory responses. The sensitivities of both Raf-1 kinase and MAP-kina se stimulation by Ang II to the inhibitors of phosphoinositide kinases, wor tmannin and LY 294002, suggest that inositol phospholipids may play a role in these activation events unrelated to their role in Ca2+ signaling. To in vestigate 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 he lp to further clarify the complex role of these lipids in initiating Ca2+-d ependent and -independent signaling responses.