Timolol movement across isolated iris-ciliary body of albino rabbit.

The outward (from the aqueous to the stromal side) and the inward (from the stromal to the aqueous side) movement of [14C]timolol across the isolated iris-ciliary body of the albino rabbit were studied using Ussing's chamber under short-circuit conditions and timolol concentrations of 0.025-60 microM. The tissue permeability in both directions decreased gradually as the timolol concentration was increased, while at higher concentrations tissue permeability was almost constant. This finding indicated that the timolol movement in both directions consists of passive diffusion and a possibly active mechanism, with the former contributing mainly at higher concentrations. The tissue permeability for passive diffusion was calculated as 7.2 x 10(-6) cm/second. The outward timolol movement by a possibly active mechanism was saturated against the concentrations tested. In addition, the outward timolol movement was significantly reduced by ouabain, 2,4-dinitrophenol and low temperature. These results suggested that the non-passive component of the outward timolol movement was carrier-mediated active transport, and Lineweaver-Burk plots gave the half-saturation concentration (Km) value of 0.098 microM. On the other hand, the inward timolol movement by a possible active mechanism was not saturated. Neither ouabain nor 2,4-dinitrophenol inhibited it. Thus the non-passive component of the inward timolol movement was thought to be different from that of the outward movement.