[Molecular structure of luminal diuretic receptors].
Since day to day sodium and water intake is more or less constant, the output by urinary sodium excretion is the key to maintain extracellular fluid volume within physiologic ranges. To achieve this goal, the kidneys ensure that most of the large quantities of filtered sodium are reabsorbed, a function that takes place in the proximal tubule, the loop of Henle and the distal tubule, and then the kidneys adjust the small amount of sodium that is excreted in urine in such a way that sodium balance is maintained. This adjustment occurs in the collecting duct. Three groups of diuretic-sensitive sodium transport mechanisms have been identified in the apical membranes of the distal nephron based on their different sensitivities to diuretics and requirements for chloride and potassium: 1) the sulfamoylbenzoic (or bumetanide)-sensitive Na+:K+:2CI- and Na+:CI- symporters in the thick ascending loop of Henle; 2) the benzothiadiazine (or thiazide)-sensitive Na+:CI- cotransporter in the distal tubule; and 3) the amiloride-sensitive Na+ channel in the collecting tubule. The inhibition of any one of these proteins by diuretics results in increased sodium urinary excretion. Recently, the use of molecular biology techniques, specially the functional expression cloning in Xenopus laevis oocytes, has led to the identification of cDNA's encoding members of the three groups of diuretic-sensitive transport proteins. The present paper reviews the primary structure and some aspects of the relationship between structure and function of these transporters as well as the new protein families emerging from these sequences. It also discusses the future implications of these discoveries on the physiology and pathophysiology of kidney disease and sodium retaining states.
Gamba
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Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de la Nutrición Salvador Zubirán, México, D.F.
D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D004231:Diuresis / Q000502:physiology*; D004232:Diuretics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D017136:Ion Transport; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009399:Nephrons / Q000378:metabolism*; D011522:Protons; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
D004232:Diuretics; D011522:Protons; D015222:Sodium Channels; D012964:Sodium
Estructura molecular de los receptores de diuréticos luminales.