Decreases in rat brain aquaporin-4 expression following intracerebroventricular administration of an endothelin ETB receptor agonist

Aquaporins (AQPs) comprise a family of water channel proteins, some of which are expressed in brain. Expressions of brain AQPs are altered after brain insults, such as ischemia and head trauma. However, little is known about the regulation of brain AQP expression. Endothelins (ETs), vasoconstrictor peptides, regulate several pathophysiolgical responses of damaged nerve tissues via ETB receptors. To show possible roles of ETB receptors in the regulation of brain AQP expression, the effects of intracerebroventricular administration of an ETB agonist were examined in rat brain. In the cerebrum, the copy numbers of AQP4 mRNAs were highest among AQP1, 3, 4, 5 and 9. Continuous administration of 500 pmol/day Ala1,3,11,15-ET-1, an ETB selective agonist, into rat brain for 7 days decreased the level of AQP4 mRNA in the cerebrum, but had no effect on AQP1, 3, 5 and 9 mRNA levels. The level of AQP4 protein in the cerebrum decreased by the administration of Ala1,3,11,15-ET-1. Immunohistochemical observations of Ala1,3,11,15-ET-1-infused rats showed that GFAP-positive astrocytes, but not neurons, activated microglia or brain capillary endothelial cells, had immunoreactivity for AQP4. These findings indicate that activation of brain ETB receptors causes a decrease in AQP4 expression, suggesting that ET down-regulates brain AQP4 via ETB receptors.