EFFECT OF TAURINE ON CHELERYTHRINE INHIBITION OF CALCIUM-UPTAKE AND ATPASE ACTIVITY IN THE RAT RETINA

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.