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|dc.identifier.citation||Current Pharmaceutical Design, 2007; 13(31):3212-3221||en|
|dc.description.abstract||Aquaporins (AQPs) are expressed in physiologically essential tissues and organs in which edema and fluid imbalances are of major concern. Potential roles in brain water homeostasis and edema, angiogenesis, cell migration, development, neuropathological diseases, and cancer suggest that this family of membrane proteins is an attractive set of novel drug targets. A problem in pursuing therapeutic and basic research strategies for dissecting contributions of AQPs to cell and tissue functions is that little is known regarding the pharmacology of AQP channels; currently defined agents such as tetraethylammonium and phloretin as blockers for aquaporins suffer from a lack of specificity and potency. Subtypes of AQPs modulated by signaling pathways could enable discrete localized control of fluid homeostasis, volume and morphology in cells and intracellular organelles, and might be found to participate in many different aspects of physiology, such as the control of paracellular permeability, process extension, growth, migration, and other responses involving changes in cell shape or surface to volume ratios. Recognizing that AQP1 is a water channel and, under permissive conditions, also a cGMP-gated cation channel, evidence in various tissues for a coupling of the cGMP signaling cascade to a physiological outcome that might involve AQP1 dual ion-and-water channel functions is of interest. Groundbreaking advances in defining aquaporin gating mechanisms suggest conformational changes are important elements in regulation and gating across classes of aquaporins. With a rapidly expanding knowledge of aquaporin structure and functional regulation, new avenues for manipulation of aquaporin channels are likely to be discovered. In parallel, a discovery for novel compounds with specificity and potency for aquaporins is a compelling goal. The need for pharmacological agents to dissect the roles of aquaporins in physiological and pathological processes is a clear call for further research in the field.||en|
|dc.publisher||Bentham Science Publ Ltd||en|
|dc.subject||Brain; Animals; Humans; Water; Aquaporins; Ion Channels; Cyclic GMP; Drug Delivery Systems; Signal Transduction; Drug Design; Aquaporin 1||en|
|dc.title||Functional domains of aquaporin-1: Keys to physiology and targets for drug discovery||en|
|dc.identifier.orcid||Yool, A. [0000-0003-1283-585X]||en|
|Appears in Collections:||Molecular and Biomedical Science publications|
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