Quantitative analysis of the combination dose-effects of taurine and taurine analogues on the phosphorylation of an approximately 44-Kd protein present in a mitochondrial subfraction of rat heart.
Combinations of taurine and analogues of taurine that partially contain the N-C-C-S moiety within a semirigid saturated ring structure were tested for their effects on the phosphorylation of an approximately 44-Kd protein present in the mitochondrial fraction of rat heart. (+/-)Piperidine-3-sulfonic acid (PiP), an inhibitor of the phosphorylation of the approximately 44-Kd protein with activity approximately similar to that of taurine, was observed to be mutually exclusive with taurine, i.e., to have a similar mode of action. The combination of taurine plus PiP in a fixed ratio mixture of 1:1 was slightly antagonistic at all concentrations. (+/-)Aminotetrahydrothiopyran-1,1-dioxide (APS), a sulfone derivative of taurine with a net positive charge, also has approximately the same inhibitory activity as taurine. However, APS was mutually nonexclusive with taurine when tested in combination and thus appears to act independently of taurine. Taurine plus APS in a fixed ratio mixture of 3:1 was highly antagonistic at low concentrations of the mixture, approached an additive relation at 50% saturation, and became synergistic at high concentrations of the mixture. Three analogues of taurine, pyridine-3-sulfonic acid (PyS), quinoline-8-sulfonic acid (QS), and 2-aminobenzenesulfonic acid (ABS), that have the basic taurine structure (N-C-C-S) partially in a semirigid unsaturated ring structure stimulate the phosphorylation of the approximately 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, QS, or ABS was titrated in the presence of a fixed concentration of taurine (10 mM), there was a competitive relation even though their electronic nature is quite different than that of taurine. The combination of QS plus PyS (1:5) appears to progress through a transition from being synergistic at low concentrations of the fixed ratio mixture, additive at 50% saturation, and finally antagonistic at high concentration of the fixed ratio mixture.
Lombardini
J B
JB
Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D010750:Phosphoproteins; D013654:Taurine