title: Efflux and accumulation of amino nitrogen in relation to the volume of rat renal inner medullary cells exposed to media of variable osmolality.
abstract: The rate of efflux of 2-amino[14C]isobutyric acid (AIB) from pre-loaded slices of rat renal inner medulla has been followed during incubation in media whose osmolality was varied between 350 and 2500 mosmol/kg H2O by adjustment of NaCl and urea concentrations. Efflux was biphasic, and it was assumed that the second, slower phase represented mainly cellular loss of AIB. As a function of cell volume (water content) the mean net rate of 2nd phase efflux declined far more abruptly (-36%) during an increase in external osmolality from 350 to 720 mosmol/kg than during further increase to 2500 mosmol/kg, over which range the rate of efflux fell by only a further 12%. Conversely, relative decrements of steady-state cell water contents during these two transitions were -17% and -37%, respectively. It is probable that in strongly hyperosmolal media (above 720 mosmol/kg) reduction in the rate of amino acid catabolism, with resultant cellular accumulation, becomes more important than passive efflux as a determinant of cell amino nitrogen content, and that this is caused by the enzyme-destabilizing effect of high intracellular concentrations of permeant urea. This interpretation is supported by the finding in the present study that trimethylamine N-oxide, which is known to counteract the destabilizing effect of urea, completely inhibited the accumulation of amino nitrogen (ninhydrin-positive substances) in media stronger than 720 mosmol/kg, as well as leading to further reduction of steady-state cell water contents, but was without effect on either variable in more dilute media. It is proposed that, under the conditions of this investigation, amino acids contribute to cell volume maintenance mainly by efflux and by metabolic accumulation under mildly and strongly hyperosmolal conditions, respectively, and that this interpretation is consistent with recent findings on the fluctuations in medullary levels of Na+, urea and total amino nitrogen in the intact kidneys of rats during acute water diuresis and oliguria (Law, R.O. (1991) Pflügers Arch. 418, 442-446).
authors.affiliation: Department of Physiology, University of Leicester, U.K.
authors.forename: R O
authors.initials: RO
authors.lastname: Law
mesh_terms: D000588:Amines / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D008536:Meglumine / Q000494:pharmacology; D008744:Methylamines / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014508:Urea / Q000494:pharmacology; D014867:Water / Q000378:metabolism
chemical_list: D000588:Amines; D000621:Aminoisobutyric Acids; D008744:Methylamines; D014867:Water; C100049:2-aminoisobutyric acid; D014268:Trifluoperazine; D012965:Sodium Chloride; D004533:Egtazic Acid; D008536:Meglumine; D014508:Urea; C005855:trimethyloxamine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid