ABSTRACT
Fluid homeostasis in the body is well known to be regulated by ion channels and transporters, but equally important are the co-expressed classes of aquaporin (AQP) water channels that facilitate transmembrane water movement. e eld of AQP
CONTENTS Abstract 273 14.1 Introduction 274 14.2Overview of Aquaporin Channel Functions in Brain Fluid
Homeostasis and Cell Migration274 14.2.1AQP4 in Cerebral Edema 275 14.2.2AQP1 in Cell Migration 277
14.3Small Molecule Drug Discovery for Aquaporin Channels 278 14.4Translational Promise of Pharmacological Modulators of Aquaporin
Channels in Brain Edema, Cancer and Other Disorders281 14.4.1Targeting AQP4 Channels in Brain Edema 281 14.4.2Dierential Regulation of Expression of AQP Channel
Types in Cancer Cells281 14.4.3Targeting AQP1 Channels in Cell Migration and Metastasis 283
14.5New Avenues for Aquaporin Drug Discovery from Traditional and Alternative Medicines 284
References 287
pharmacology is expanding rapidly with the new identication of small molecule druglike agents with distinctive properties in AQP modulation, allowing exploration of potential therapeutic applications in brain edema, cancer and other disorders. Pharmacological agents could modulate AQPs by direct occlusion of the water pore itself, by acting at distinct sites that confer other channel properties, or by altering levels of protein expression or membrane targeting. Expanding the pharmacological portfolio will benet basic research and promote new therapeutic strategies in many conditions involving AQPs in the symptoms or disease processes. Exploring herbal alternative medicines as sources of pharmacological agents for AQPs is likely to have a substantial impact on the eld of AQP research, which has keenly awaited the development of chemical interventions as a platform for therapeutic approaches. Recent work is providing an enhanced understanding of the molecular mechanisms of action of traditional herbal medicines as novel sources of AQP modulators.
