Angiotensin II activates distinct signal transduction pathways in astrocytes isolated from neonatal rat brain

✍ Scribed by E. Ann Tallant; June T. Higson

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 134 KB
• Volume: 19
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(199704)19:4<333::aid-glia6>3.0.co;2-y

✦ Synopsis

In previous studies, we showed that angiotensin II (Ang II) and its congener peptides-angiotensin-(2-8) ] and angiotensin-(1-7) [Ang-(1-7)]activate 2 distinct signal transduction pathways in a mixed population of human cortical astrocytoma cells. This suggested that different populations of astrocytes could be heterogeneous with respect to their expression of Ang II receptors or the responses to which these receptors are coupled. To compare the responses which are activated by Ang II and its congener peptides in astrocytes from different brain regions, we measured phospholipase C (PLC) activity and prostaglandin release in isolated astrocytes from 4 different areas of neonatal rat brain. In medullary and cerebellar astrocytes, Ang II activated a phosphoinositide-specific PLC in a dose-dependent manner with EC 50 s of 1.74 and 1.86 nM, respectively. Ang-(2-8) also caused an increase in inositol phosphate release. PLC activity was coupled to an AT 1 receptor in both medullary and cerebellar astrocytes, as demonstrated by the inhibition of Ang II-activation of inositol phosphate release by the AT 1 antagonist losartan. The AT 2 antagonist PD 123319 was ineffective. Ang II and Ang-(2-8) also released prostacyclin from medullary and cerebellar astrocytes, measured as the release of its stable metabolite 6-keto-PGF 1a . In contrast, Ang II did not activate PLC or release prostaglandins in astrocytes isolated from the cortex or hypothalamus. In addition, Ang-(1-7) did not stimulate the release of inositol phosphates or prostacyclin in astrocytes from any of the neonatal rat brain regions examined. However, bradykinin (1 µM) activated PLC or released prostacyclin in astrocytes isolated from all 4 brain regions. These results suggest that Ang II receptors on region-specific astrocytes activate distinct signal transduction mechanisms in response to different angiotensin peptides.