QUANTITATIVE-ANALYSIS OF THE COMBINATION DOSE-EFFECTS OF TAURINE AND TAURINE ANALOGS ON THE PHOSPHORYLATION OF AN SIMILAR-TO-44-KD PROTEIN PRESENT IN A MITOCHONDRIAL SUBFRACTION OF RAT-HEART

Combinations of taurine and analogues of taurine that partially contai n the N-C-C-S moiety within a semirigid saturated ring structure were tested for their effects on the phosphorylation of an similar to 44-Kd protein present in the mitochondrial fraction of rat heart. (+/-)Pipe ridine-3-sulfonic acid (PiP), an inhibitor of the phosphorylation of t he similar to 44-Kd protein with activity approximately similar to tha t of taurine, was observed to be mutually exclusive with taurine, i.e. , to have a similar mode of action. The combination of taurine plus Pi P in a fixed ratio mixture of 1:1 was slightly antagonistic at all con centrations. (+/-)Aminotetrahydrothiopyran-1,1-dioxide (APS), a sulfon e derivative of taurine with a net positive charge, also has approxima tely the same inhibitory activity as taurine. However, APS was mutuall y nonexclusive with taurine when tested in combination and thus appear s to act independently of taurine. Taurine plus APS in a fixed ratio m ixture of 3:1 was highly antagonistic at low concentrations of the mix ture, approached an additive relation at 50% saturation, and became sy nergistic at high concentrations of the mixture. Three analogues of ta urine, pyridine-3-sulfonic acid (PyS), quinoline-8-sulfonic acid (QS), and 2-aminobenzenesulfonic acid (ABS), that have the basic taurine st ructure (N-C-C-S) partially in a semirigid unsaturated ring structure stimulate the phosphorylation of the similar to 44-Kd protein, Due to the unsaturated ring structure, these analogues of taurine have a net negative charge at physiologic pH and are not zwitterions. When PyS, Q S, or ABS was titrated in the presence of a fixed concentration of tau rine (10 mM), there was a competitive relation even though their elect ronic nature is quite different than that of taurine. The combination of QS plus PyS (1:5) appears to progress through a transition from bei ng synergistic at low concentrations of the fixed ratio mixture, addit ive at 50% saturation, and finally antagonistic at high concentration of the fixed ratio mixture.