[Water homeostasis in the living: molecular organization, osmoregulatory reflexes and evolution]

Abstract

Human body weight is about 70% water; 55% of the water are in cells and 45% in extracellular compartments, mainly body fluids. Each compartment has its own osmoregulatory system. The mechanisms of intracellular osmoregulation likely appeared with the cell itself, i.e. in primitive prokaryotes, some 3.8 billions years ago. Osmotic stress responses observed in present-day bacteria, yeast, plant and animals cells in culture are very similar. Variations in the cell volume entail an extension or retraction of plasma membrane that activates mechanically-gated ion channels or mechanoreceptors. Some of them have been cloned from E. coli, the nematode C. elegans, the drosophila. Osmotic stress determines an intracellular cascade of transactivations, the last transcription factor binding to a Tonicity response element (TonE) of osmoprotective genes. These genes encode enzymes synthesizing compatible osmolytes that reequilibrate the osmotic pressure. Volume and osmolality of the biological fluids (le milieu intérieur) are regulated by neuroendocrine reflexes involving an afferent neural limb from baro- and osmo-receptors to hypothalamus and an efferent endocrine limb from neurosecretory cells to target cells, the hydroosmotic cells localized in osmoregulatory organs. Afferent signals trigger the biosynthesis and the processing of neurohypophyseal preprohormones in magnocellular neurons of the supraoptic and paraventricular nuclei of hypothalamus. Vasopressin in mammais and vasotocin in other vertebrates, endowed with antidiuretic and antinatriuretic properties, act on hydroosmotic cells localized in the nephron collecting duct. A specific vasopressin receptor, the V2 type receptor, located in the basolateral membrane of the principal cells, is coupled with an heterotridimeric protein Gs that activates adenylate cyclase. The cAMP product, in turn, stimulates the protein kinase A (PKA). The latter mobilizes 5 effectors located in the apical membrane: 1) the water channel aquaporin 2; 2) the urea transporter UT1; 3) the amiloride-sensitive sodium channel ENaC; 4) the inward-rectifying potassium channel ROM-K1; 5) the chloride channel CFTR. Modulation of each effector is ensured by an A kinase anchoring protein (AKAP). The effectors are transported from cytosol to apical membrane through transport vesicles equipped with membrane fusion proteins (such as VAMP2) that recognize specific apical membrane proteins (such as syntaxins). Water flows into principal cells from collecting duct lumen through AQP2 and flows out to interstitium through AQP3 and AQP4 and finally reachs blood circulation through AQP1 capillaries. Vasopressin orchestrates the live effectors so as to keep water and solutes reabsorptions in balance with volaemia and osmolality set points.