Abstract
Taurine stimulates ATP-dependent Ca2+ uptake in the rat rod outer segments (ROS). This stimulation has been linked to the function of the cyclic nucleotide-gated cation channel, implying an important physiologic role for taurine in visual signal transduction. Calmodulin (CaM) has been reported to affect taurine transport in the choroid plexus and also to inhibit the cyclic nucleotide-gated channel; thus, the effects of the competitive CaM inhibitors trifluoperazine (TFP) andN-(8-aminooctyl)-5-iodonaphthalene-1-sulfonamide (J-8) were studied on Ca2+ and taurine uptake in the rat ROS. Pretreatment of the ROS preparation with TFP and J-8 for 5 min before measurement of Ca2+-uptake activity produced inhibition of the effects of taurine on ATP-dependent Ca2+ uptake. Both TFP and J-8 also were effective in inhibiting high-affinity taurine uptake. In both uptake systems, inhibition by TFP was noncompetitive. These data initially suggested that the stimulatory effects of taurine on ATP-dependent Ca2+ uptake are dependent on taurine uptake. However, competitive inhibition of taurine uptake by guanidinoethane sulfonate did not produce any effect on the stimulatory effects of taurine. Previous studies have proposed that taurine binds directly to the plasma membrane, and our study demonstrated that TFP inhibits taurine binding to the ROS. In addition, our study demonstrated that taurine uptake is unaffected by varying the concentration of Ca2+ and that the effects of TFP are independent of Ca2+, suggesting that TFP acts through a CaM-independent mechanism.
Footnotes
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Send reprint requests to: John B. Lombardini, Ph.D., Department of Pharmacology, Texas Tech University Health Sciences Center, 3601 4th St., Lubbock, TX 79430. E-mail: PHRJBL{at}TTUHSC.edu
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↵1 This work was supported in part by grants from the RGK Foundation of Austin, Texas, and the Taisho Pharmaceutical Co., Ltd., of Tokyo, Japan.
- Abbreviations:
- ROS
- rod outer segments
- CNG
- cyclic nucleotide-gated
- CaM
- calmodulin
- TFP
- trifluoperazine
- J-8
- N-(8-aminooctyl)-5-iodonaphthalene-1-sulfonamide
- GES
- guanidinoethane sulfonate
- KRB
- Krebs-Ringer-bicarbonate
- BCA
- bicinchoninic acid
- Received March 16, 1999.
- Accepted May 28, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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