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Protein kinase G is involved in ammonia‐induced swelling of astrocytes
Author(s) -
Konopacka Agnieszka,
Konopacki Filip A.,
Albrecht Jan
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.05802.x
Subject(s) - astrocyte , in vivo , protein kinase a , swelling , ammonia , chemistry , cell , kinase , biology , microbiology and biotechnology , endocrinology , biochemistry , medicine , pathology , central nervous system
Ammonia‐induced swelling of astrocytes is a primary cause of brain edema associated with acute hepatic encephalopathy. Previous studies have shown that ammonia transiently increases cGMP in brain in vivo and in cultured astrocytes in vitro . We hypothesized that protein kinase G (PKG), an enzyme activated by cGMP and implicated in regulation of cell shape, size, and/or volume in peripheral and CNS cells, may play a role in the ammonia‐induced astrocytic volume increase. Treatment of cultured rat cortical astrocytes with 1 or 5 mM NH 4 Cl (ammonia) for 24 h increased their cell volume by 50% and 80% above control, respectively, as measured by confocal imaging followed by 3D computational analysis. A cGMP analog, 8‐(4‐chlorophenylthio)‐cGMP, increased the cell volume in control cells and potentiated the increase in 1 mM ammonia‐treated cells. A soluble guanylate cyclase inhibitor (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one) abrogated, and a PKG inhibitor [8‐(4‐chlorophenylthio)‐cGMP‐thioate, Rp‐isomer] dose‐dependently reduced the cell volume‐increasing effect of 5 mM ammonia. The results suggest that (i) PKG may play a permissive role in ammonia‐induced astrocytic swelling and (ii) elevation of brain cGMP associated with acute exposure to ammonia in vivo may aggravate the ensuing brain edema.