Effect of acetazolamide on aquaporin-1 and fluid flow in cultured choroid plexus.

Abstract

Acetazolamide (AZA), used in treatment of early or infantile hydrocephalus, is effective in some cases, while its effect on the choroid plexus (CP) remains ill-defined. The drug reversibly inhibits aquaporin-4 (AQP4), the most ubiquitous "water pore" in the brain, and perhaps modulation of AQP1 (located apically on CP cells) by AZA may reduce cerebrospinal fluid (CSF) production. We sought to elucidate the effect of AZA on AQP1 and fluid flow in CP cell cultures.CP tissue culture from 10-day Sprague-Dawley rats and a TRCSF-B cell line were grown on Transwell permeable supports and treated with 100 μM AZA. Fluid assays to assess direction and extent of fluid flow, and AQP1 expression patterns by immunoblot, Immuncytochemistry (ICC), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) were performed.Immunoblots and ICC analyses showed a decrease in AQP1 protein shortly after AZA treatment (lowest at 12 h), with transient AQP1 reduction mediated by mRNA expression (lowest at 6 h). Transwell fluid assays indicated a fluid shift at 2 h, before significant changes in AQP1 mRNA or protein levels.Timing of AZA effect on AQP1 suggests the drug alters protein transcription, while affecting fluid flow by a concomitant method. It is plausible that other mechanisms account for these phenomena, as the processes may occur independently.

• Authors: Pouya A Ameli, Meenu Madan, Srinivasulu Chigurupati, Amin Yu, Sic L Chan, Jogi V Pattisapu
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 113 Pg. 59-64 ( 2012) ISSN: 0065-1419 [Print] Austria
• PMID: 22116425 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbonic Anhydrase Inhibitors
• Dextrans
• RNA, Messenger
• Rhodamines
• dextran tetramethylrhodamine
• Aquaporin 1
• Acetazolamide

Topics

• Acetazolamide (pharmacology)
• Animals
• Animals, Newborn
• Aquaporin 1 (metabolism)
• Capillary Permeability (drug effects)
• Carbonic Anhydrase Inhibitors (pharmacology)
• Choroid Plexus (drug effects, metabolism)
• Dextrans
• Gene Expression Regulation (drug effects)
• Hydrodynamics
• Organ Culture Techniques
• RNA, Messenger (metabolism)
• Rats
• Rhodamines
• Time Factors