F. Blomstrand et al., Distinct pharmacological properties of ET-1 and ET-3 on astroglial gap junctions and Ca2+ signaling, AM J P-CELL, 277(4), 1999, pp. C616-C627
Astrocytes represent a major target for endothelins (ETs), a family of pept
ides that have potent and multiple effects on signal transduction pathways
and can be released by several cell types in the brain. In the present stud
y we have investigated the involvement of different ET receptor subtypes on
intercellular dye diffusion, intracellular Ca2+ homeostasis, and intercell
ular Ca2+ signaling in cultured rat astrocytes from hippocampus and striatu
m. Depending on the ET concentration and the receptor involved, ET-1- and E
T-3-induced intracellular Ca2+ increases with different response patterns.
Both ET-1 and ET-3 are powerful inhibitors of gap junctional permeability a
nd intercellular Ca2+ signaling. The nonselective ET receptor agonist saraf
otoxin S6b and the ETB receptor-selective agonist IRL 1620 mimicked these i
nhibitions. The ET-3 effects were only marginally affected by an ETA recept
or antagonist but completely blocked by an ETB receptor antagonist. However
, the ET-1-induced inhibition of gap junctional dye transfer and intercellu
lar Ca2+ signaling was only marginally blocked by ETA or ETB receptor-selec
tive antagonists but fully prevented when these antagonists were applied to
gether. The ET-induced inhibition of gap junction permeability and intercel
lular Ca2+ signaling indicates that important changes in the function of as
troglial communication might occur when the level of ETs in the brain is in
creased.