Sulfone analogues of taurine as modifiers of calcium uptake and protein phosphorylation in rat retina.
The syntheses of five sulfone analogues of taurine are described: 2-aminoethylmethyl sulfone (AEMS), thiomorpholine-1,1-dioxide (TMS), N-methylthiomorpholine-1,1-dioxide (M-TMS), (+/-)3-aminotetrahydrothiopyran-1,1-dioxide (APS), and (+/-)3-aminotetrahydrothiophene-1,1-dioxide (ATS). When these compounds were evaluated in the rat retina as modulators of ATP-dependent calcium ion uptake at low calcium ion concentrations (10 microM), AEMS, ATS, and APS were found to be more potent stimulators of ATP-dependent calcium ion uptake than taurine. TMS and M-TMS had no effect. At high concentrations of calcium ions (1.44 mM), taurine, AEMS, ATS, APS, and TMS inhibited ATP-independent calcium ion uptake; AEMS, ATS, and APS were more potent inhibitors than taurine. ATS was the only compound tested (including taurine) that inhibited ATP-dependent calcium ion uptake at high calcium ion concentrations. The effects of the sulfone analogues of taurine on the incorporation of phosphate into retinal proteins were also studied. Taurine, AEMS, ATS, APS, and TMS were equipotent inhibitors of phosphate incorporation (30-45%). M-TMS had no effect.
Liebowitz
S M
SM
Division of Medicinal Chemistry, College of Pharmacy, University of Texas, Austin 78712.
Lombardini
J B
JB
Allen
C I
CI
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000494:pharmacology*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology*
D011506:Proteins; D013450:Sulfones; D013654:Taurine; D000255:Adenosine Triphosphate; D002118:Calcium