Taurine stimulation of calcium uptake in the retina: Mechanism of action.

摘要

Taurine is a free amino acid found in millimolar concentrations inside most animal cells. The retina appears to possess the greatest amount of taurine compared to the other cell types. Taurine modulates calcium uptake in retinal tissue with millimolar potency, suggesting that the physiologic function of taurine maybe related to calcium. Inside the cell, calcium levels are low compared to the outside, and interestingly, taurine is known to stimulate calcium uptake in the presence of low calcium levels (∼10–500 μM) in the presence of ATP, perhaps implying a regulatory role for taurine intracellularly. The mechanism behind this effect of taurine was studied. Chelerythrine (CHT) is a potent protein kinase C (PKC) and ATPase inhibitor that inhibited the effects of taurine to stimulate calcium uptake, and it was used to help define the mechanism of taurine stimulation. CHT inhibits ATPase activity in the retina and so ATPase activity in the retina was studied. Taurine had no direct effect on ATPase activity and thus, the involvement of ATPase activity was discounted. CHT also inhibited taurine uptake and the need for taurine uptake relative to its effects was studied. Inhibition of taurine uptake with taurine analogues surprisingly did not produce any effects, eliminating taurine uptake as a necessary event in the mechanism of action behind taurine stimulation, and basically leaving taurine binding to membranes as the site of action. The involvement of ion channel activation was also studied. The inhibition of cGMP-gated channels antagonized the effects of taurine, strongly suggesting that taurine exerts a positive effect on this channel to increase calcium uptake. Lastly, the effect of taurine on calcium binding was studied as taurine modulates calcium binding in the sarcolemma and may in fact modulate binding and not uptake in the retina. Taurine did not affect binding which leads to its effects being directed to calcium uptake. The mechanism of taurine, thus, can be summarized: Taurine binds to membranes to modulate the activation of calcium channels and increase calcium uptake, a process which does not involve ATPase activity, taurine uptake or calcium binding.