SITE OF ORIGIN OF AN URINARY NA-K-CL COTRANSPORT INHIBITOR

We investigated the site of origin of a potent inhibitor of the Na-K-C l cotransport system (CIF), which has been previously identified in ur ines from salt-loaded rats. Rats were given a 2% NaCl solution to drin k for 15 and 60 days and the plasma was obtained and tested for cotran sport inhibitory activity (on bumetanide-sensitive Li+ efflux in Li-lo aded human erythrocytes) in dose-response curves. The IC50 for cotrans port inhibition (vol:vol dilution reducing cotransport activity by 50% ) was found to be 26.5 +/- 7.2 (mean +/- SEM, n = 5) and 6.9 +/- 0.7% (n = 10) on days 15 and 60, respectively (control samples, day 0, only inhibited about 20% cotransport activity at a 30% plasma vol:vol dilu tion, n = 7). Organ extracts from salt-loaded rats were prepared and t ested for cotransport inhibitory activity. A statistically significant cotransport inhibitory activity was only found in pituitary extracts (-36 +/- 3 vs. -5 +/- 4% in control rats, n = 4, p < 0.01), Dissection of a large number of pituitary glands from salt-loaded rats revealed CIF activity only in the neurohypophysis (cotransport inhibition -46.5 +/- 5.2 vs. -0.5 +/- 16.4% in the anterior lobe, n = 4, p < 0.05). In conclusion, CIF is a new circulating endogenous factor, probably secr eted by the neurohypophysis.