Cyclosporine-A transport in isolated renal proximal tubular cells: inhibition by calcium channel blockers.

We have studied the transport characteristics of cyclosporine A (CSA) in isolated rabbit renal proximal tubular cells (PTC). The uptake as well as efflux was very rapid and dependent on temperature. PTC accumulated CSA by several fold above the incubation medium concentration. Kinetic analysis yielded an apparent Km and Vmax values of 5.1 microM and 47 Pmoles/10(6) cells/min respectively. Calcium channel blockers verapamil or diltiazem, at concentrations (0.5-1.0 mM) that inhibited calcium uptake, reduced CSA uptake significantly. Other calcium transport modulators A23187 (5 microM), trifluoroperazine (50 microM) and ruthenium red (100 microM) induced anticipated changes in calcium uptake but had no effect on CSA uptake. These results suggest a close association or interaction between the calcium channels and the CSA transporting/binding sites on PTC membranes.