M. Tamura et al., A NOVEL ENDOGENOUS SODIUM-PUMP INHIBITOR IN PIG URINE - PURIFICATION AND COMPARISON WITH THE INHIBITOR PURIFIED FROM BOVINE ADRENAL-GLANDS, Journal of cardiovascular pharmacology, 22, 1993, pp. 190000047-190000050
To clarify the chemical nature and pathophysiological significance of
an endogenous, specific Na-pump inhibitor, extracts of various tissues
have been examined. The activities were extracted by an Amberlite XAD
-2 adsorbent and fractionated by high-performance liquid chromatograph
y (HPLC) on an ODS column. Among many tissues and fractions tested, th
e extract of pig urine has been found to contain a large amount of Rb-
86 uptake inhibitory activities. The strongest inhibitory activity for
Rb-86 influx into erythrocytes also exhibited a cross-reactivity with
anti-ouabain antibodies. This activity has been purified to homogenei
ty using five steps of reverse-phase HPLC. Although most of the dose-r
esponse curves for this purified Na-pump inhibitor, designated as urox
in, in the various assay systems paralleled those of ouabain and the i
nhibitor purified from bovine adrenal glands (designated as adrexin C)
, the cross-reactivity curve with antiouabain antibodies did not. The
retention time of uroxin on an ODS HPLC column was also different from
that of digoxin, ouabain, or adrexin C. H-1 nuclear magnetic resonanc
e spectroscopic study suggests that uroxin is a novel Na-pump inhibito
r that is structurally different from any of the known cardiotonic ste
roids or the substances previously reported to exhibit Na-pump inhibit
ory activity. Thus, uroxin may be a new type of endogenous regulator f
or the Na pump.