Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1332347 (ADH)
 2,230 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The longstanding puzzle of membrane water-permeability was advanced by discovery of a new class of proteins known as the "aquaporins" (AQPs). First identified in red blood cells, AQP1 was shown to function as a water channel when expressed in Xenopus oocytes or when pure AQP1 protein was reconstituted into synthetic membranes. Analysis of the primary sequence revealed that the two halves of the AQP1 polypeptide are tandem repeats; site directed mutagenesis studies indicate that the repeats may fold into an obversely symmetric structure which resembles an hourglass. Electron crystallography elucidated the tetrameric organization of AQP1, and functional studies suggest that each tetramer contains multiple functionally independent aqueous pores. AQP1 is abundant in the apical and basolateral membranes of renal proximal tubules and descending thin limbs, and is also present in multiple extra renal tissues. AQP2 is expressed only in the principal cells of renal collecting duct where it is the predominant vasopressin (ADH, antidiuretic hormone) regulated water channel. AQP2 is localized in the apical membrane and in intracellular vesicles which are targeted to the apical plasma membranes when stimulated by ADH. Humans with mutations in genes encoding AQP1 and AQP2 exhibit contrasting clinical phenotypes. AQP3 resides in the basolateral membranes of renal collecting duct principal cells providing an exit pathway for water; AQP4 is abundant in brain where it may function as the hypothalamic osmoreceptor responsible for secretion of ADH. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiological problems of water balance and disorders of water balance.
 ...
PMID:The aquaporin family of water channels in kidney. 898 45

The biophysical models describing the structure of water pores or channels have evolved, during the last forty years, from a pure 'black box' approach to a molecular based proposal. The initial 'sieving pore' in which water and other molecules were moving together was replaced by a more restrictive model, where water is moving alone in a 'single file' mode. Aquaporins discovery and cloning [G.M. Preston, T.P. Carroll, W.B. Guggino, P. Agre, Science 256 (1992) 365] leaded to the 'hour-glass model' and other alternative proposals, combining information coming from molecular biology experiments and two dimensional crystallography. Concerning water transfers in epithelial barriers the problem is quite complex, because there are at least two alternative pathways: paracellular and transcellular and three different driving forces: hydrostatic pressure, osmotic pressure or 'transport coupled' movements. In the case of ADH-sensitive epithelia it is more or less accepted that regulated water channels (AQP2), that can be inserted in the apical membrane, coexist with basolateral resident water channels (AQP3). The mechanism underlying the so-called 'transport associated water transfer' is still controversial. From the classical standing gradient model to the ion-water co-transport, different hypothesis are under consideration. Coming back to hormonal regulations, other than the well-known regulation by neuro-hypophysis peptides, a steroid second messenger, progesterone, has been recently proposed [P. Ford, G. Amodeo, C. Capurro, C. Ibarra, R. Dorr, P. Ripoche, M. Parisi, Am. J. Physiol. 270 (1996) F880].
 ...
PMID:Biophysical properties of epithelial water channels. 1702 8