title: Non-specific inhibitors of aquaporin-4 stimulate S100B secretion in acute hippocampal slices of rats.
abstract: Aquaporin-4 (AQP-4) is the principal brain water channel and is predominantly expressed in astrocytes suggesting its dynamic involvement in water homeostasis in brain tissue. Due to the co-localization of AQP-4 and inward rectifier K(+) channels Kir 4.1, a functional coupling between these proteins has been proposed. AQP-4 has a putative role in the physiopathology of brain disorders including epilepsy and trauma. S100B is a calcium-binding protein expressed and secreted by astrocytes, and commonly used as a parameter of astroglial activation. Here, we investigate a possible link between AQP-4 activity (and Kir 4.1) and S100B secretion in hippocampal slices of rats of different ages using non-specific inhibitors of AQP-4 (AZA, acetazolamide and TEA, tetraethylammonium) and Kir 4.1 (barium chloride). We found that blockade of AQP-4 with TEA and AZA produced an increase in S100B secretion in young rats, compatible with an astroglial activation observed in many conditions of brain injury. On the other hand, BaCl(2) induced Kir 4.1 inhibition caused a decrease in S100B secretion. Both channels, AQP-4 and Kir 4.1, exhibited a similar ontogenetic profile, in spite of the functional uncoupling, in relation to S100B secretion. Moreover, we found a significant increase in the S100B secretion basal levels with the increasing of animal age and the incubation with high levels of potassium resulted in a decrease of S100B secretion in 30 and 90-day old rats. These data, together with previous observations from gap junctions and glutamate transport of astrocytes, contribute to characterize the operational system involving astroglial activation, particularly on S100B secretion, in brain disorders.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, Porto Alegre, RS, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Zanotto
authors.forename: Renata Torres
authors.initials: RT
authors.lastname: Abib
authors.forename: Cristiane
authors.initials: C
authors.lastname: Batassini
authors.forename: Lucas Silva
authors.initials: LS
authors.lastname: Tortorelli
authors.forename: Regina
authors.initials: R
authors.lastname: Biasibetti
authors.forename: Letícia
authors.initials: L
authors.lastname: Rodrigues
authors.forename: Patrícia
authors.initials: P
authors.lastname: Nardin
authors.forename: Fernanda
authors.initials: F
authors.lastname: Hansen
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
authors.forename: Marina Concli
authors.initials: MC
authors.lastname: Leite
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D051401:Aquaporin 4 / Q000037:antagonists & inhibitors*; D017609:Barium Compounds / Q000494:pharmacology; D015153:Blotting, Western; D002712:Chlorides / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D000098854:Kcnj10 Channel
chemical_list: D051401:Aquaporin 4; D017609:Barium Compounds; D002712:Chlorides; D000098854:Kcnj10 Channel; D009414:Nerve Growth Factors; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D013757:Tetraethylammonium Compounds; C024986:barium chloride; D000086:Acetazolamide; D011188:Potassium