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© Research
Publication : Journal of neurochemistry

Coupling of ETB endothelin receptor to mitogen-activated protein kinase stimulation and DNA synthesis in primary cultures of rat astrocytes

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of neurochemistry - 01 Feb 1996

Lazarini F, Strosberg AD, Couraud PO, Cazaubon SM

Link to Pubmed [PMID] – 8592114

J. Neurochem. 1996 Feb;66(2):459-65

Astrocytes have been shown to express endothelin (ET) receptors functionally coupled, via different heterotrimeric G proteins, to several intracellular pathways. To assess the relative contribution of each subtype in the astrocytic responses to ET-1, effects of BQ123, an antagonist selective for the ET receptor subtype A (ETA-R), and IRL1620, an agonist selective for the ET receptor subtype B (ETB-R), were investigated in primary cultures of rat astrocytes. Binding experiments indicated that the ETB-R is the predominant subtype in these cells. Inhibition of forskolin-stimulated cyclic AMP production was observed under. ETB-R stimulation. Bordetella pertussis toxin (PTX) pretreatment completely abolished this effect, indicating that this pathway is coupled to the ETB-R via Gi protein. Increases of tyrosine phosphorylation of cellular proteins, stimulation of mitogen-activated protein kinase (MAPK), and DNA synthesis were also found to be mediated by the ETB-R, but through PTX-insensitive G protein. IRL1620-induced MAPK activation involved the adapter proteins Shc and Grb2 and the serine/threonine kinase Raf-1. This study reveals that the various effects of ET-1 in astrocytes are mediated by the ETB-R, which couples to multiple signaling pathways including the MAPK cascade.

http://www.ncbi.nlm.nih.gov/pubmed/8592114