Jd. Militante et Jb. Lombardini, EFFECT OF TAURINE ON CHELERYTHRINE INHIBITION OF CALCIUM-UPTAKE AND ATPASE ACTIVITY IN THE RAT RETINA, Biochemical pharmacology, 55(5), 1998, pp. 557-565
Taurine potentiates calcium uptake in whole retinal homogenates as wel
l as in rod outer segments and mitochondrial fractions. The aim of thi
s study was to correlate taurine potentiation of calcium uptake with i
ts effects on other cellular processes through the use of chelerythrin
e (CHT), a modulator of protein kinase C (PKC), ATPase activity, and,
as recently shown, of retinal protein phosphorylation. CHT inhibited c
alcium uptake only when ATP was present, and inhibition increased sign
ificantly in conditions of ATP excess. Taurine potentiated ATP-depende
nt calcium uptake but decreased the potency of ATP to induce uptake ac
tivity. CHT inhibition of calcium uptake exhibited similar potencies i
n the presence and absence of taurine, and this inhibition seemed to b
e independent of PKC inhibition. Because of the ATP-dependence of the
observed effect, total ATPase activity was studied using similar treat
ments. In the absence of taurine, CHT inhibited ATPase activity with t
he same potency (IC(50)similar to 59.3 mu M) as with calcium uptake in
hibition (IC(50)similar to 87.9 mu M), presenting a possible mechanism
of action of CHT. In the presence of taurine, no such correlation was
observed, suggesting an ATPase-independent mechanism of action. In fa
ct, taurine did not potentiate ATPase activity, but rather it decrease
d the potency of CHT inhibition of ATPase, effects incongruent with th
e effects of taurine on calcium uptake and on CHT inhibition of calciu
m uptake. Enzyme kinetic experiments provided more supporting data. Ta
urine was found to cause an increase in the affinity of the ATP substr
ate for the ATPase enzyme, contradicting the aforementioned effect of
taurine to decrease the potency of ATP to induce calcium uptake. Thus,
taurine seems to increase calcium uptake through a hitherto unreporte
d mechanism distinct from its modulation of ATPase activity. (C) 1998
Elsevier Science Inc.