It is well known that different oxovanadium species can have significantly different
biopotencies, including hypoglycemic actions. The basis for the observed differences
in the biopotency of different oxovanadium species: vanadate, vanadyl, 1,10-phenanthroline
bisperoxovanadate (phen-bpv), 4-methyl 1,10-phenanthroline bisperoxovanadate (mpv)
and 4,7-dimethyl 1,10-phenanthroline bisperoxovanadate (dpv), was examined in this
study. The cellular uptake kinetics for these oxovanadium species was measured. Phen-bpv
and vandyl had the most rapid cellular uptake. Mpv, dpv and vanadate exihibited a
much slower uptake kinetics. Stimulation of protein tyrosine phosphorylation (PTP),
both the time dependency and the dose dependency, was used as an index for biopotency.
Although phen-bpv and vanadyl had the same cellular uptake kinetics, they differed
markedly in their ability to stimulate PTP. Structurally similar oxovanadium species,
phen-bpv, mpv and dpv demonstrated different uptake kinetics and effects on stimulating
PTP. Bioavailability, both in term of cellular uptake and migration or transport to
the active site, has been shown to be an important factor, in addition to intrinsic
activity of the oxovanadium species, in determining the overall biopotency. Finally,
this study demonstrates that variation of the chelating ligand has a profound effect
on the physiochemical properties and biological effects of the oxovanadium species.
Key words
Oxovanadium Compounds - Cellular Uptake - Insulin Mimetics
