Endothelins decrease the expression of aquaporins and plasma membrane water permeability in cultured rat astrocytes.

Some of the aquaporins (AQPs), a family of water channel proteins, are expressed in astrocytes. The expression of astrocytic AQPs is altered after brain insults, such as ischemia and head trauma. However, little is known about the regulation of AQP expressions. Endothelins (ETs), which are vasoconstrictor peptides, regulate several pathophysiological responses of astrocytes. In this study, the effects of ETs on AQP expressions and plasma membrane water permeability were examined in cultured rat astrocytes. Determination of AQP mRNA copy numbers revealed that AQP1 and AQP4 were expressed prominently in cultured astrocytes. ET-1 (100 nM) and Ala¹,³,¹¹,¹⁵-ET-1 (an ETB receptor agonist, 50 nM) decreased the AQP4 and AQP9 mRNA levels in cultured astrocytes, but the AQP1, -3, -5, and -8 mRNA levels remained unchanged. BQ788, an ETB receptor antagonist, reduced the effects of ET-1 on astrocytic AQP mRNAs, whereas FR139317, an ETA antagonist, had no effect. Immunoblot analyses revealed that treatment with ET-1 decreased the protein contents of AQP4 and AQP9 in both total cell lysates and plasma membrane fractions of cultured astrocytes. ET-1 and Ala¹,³,¹¹,¹⁵-ET-1 decreased hypoosmolarity-induced water influxes into cultured astrocytes. In the presence of 30 μM Hg²+, which inhibits water movement through AQP1 and AQP9, the hypoosmolarity-induced water influxes were reduced. Phloretin, an inhibitor of AQP9, did not greatly affect the water influxes. The ET-induced decreases in water influxes were obtained in the presence of Hg²+ and phloretin. These results suggest that ET is a factor that regulates AQP expressions and water permeability in astrocytes.

Tanaka K ，Koyama Y 《-》

Decreases in rat brain aquaporin-4 expression following intracerebroventricular administration of an endothelin ET B 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 pathophysiological responses of damaged nerve tissues via ET(B) receptors. To show possible roles of ET(B) receptors in the regulation of brain AQP expression, the effects of intracerebroventricular administration of an ET(B) 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 Ala(1,3,11,15)-ET-1, an ET(B) 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 Ala(1,3,11,15)-ET-1. Immunohistochemical observations of Ala(1,3,11,15)-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 ET(B) receptors causes a decrease in AQP4 expression, suggesting that ET down-regulates brain AQP4 via ET(B) receptors.

Koyama Y ，Tanaka K 《-》

Intracerebroventricular administration of an endothelin ETB receptor agonist increases expression of tissue inhibitor of matrix metalloproteinase-1 and -3 in rat brain.

Koyama Y ，Baba A ，Matsuda T 《NEUROSCIENCE》

Regulation of brain aquaporins.

Gunnarson E ，Zelenina M ，Aperia A 《NEUROSCIENCE》

Hyperosmotic induction of aquaporin expression in rat astrocytes through a different MAPK pathway.

Water homeostasis of the nervous system is important during neural signal transduction. Astrocytes are crucial in water transport in the central nervous system under both physiological and pathological conditions. To date, five aquaporins (AQP) have been found in rat brain astrocytes. Most studies have focused on AQP4 and AQP9, however, little is known about the expression of AQP3, -5, and -8 as well as their regulating mechanism in astrocytes. The expression patterns of AQP3, -5, and -8 in astrocytes exposed to hyperosmotic solutions were examined to clarify the roles of AQP3, -5, and -8 in astrocyte water movement. The expression of AQP4 and AQP9 under the same hyperosmotic conditions was also investigated. The AQP4 and AQP9 expressions continuously increased until 12 h after hyperosmotic solution exposure, whereas the AQP3, -5, and -8 expressions continued to increase until 6 h after hyperosmotic solution exposure. The different AQPs decreased at corresponding time points (24 h for AQP4 and AQP9; 12 h for AQP3, -5, and -8 after hyperosmotic solution exposure). The ERK inhibitor can attenuate the expression of AQP3, -5, and -8 after hyperosmotic solution exposure. The p38 inhibitor can inhibit the AQP4 and AQP9 expressions in cultured astrocytes. AQP expression is directly related to the extracellular hyperosmotic stimuli. Moreover, different AQPs can be regulated by a distinct MAPK signal transduction pathway.

Yang M ，Gao F ，Liu H ，Yu WH ，Zhuo F ，Qiu GP ，Ran JH ，Sun SQ ... -  《-》