TRANSPORT OF SALICYLIC ACID BY THE CHOROID PLEXUS IN VITRO

It is possible that salicylate may compete with therapeutically important drugs and acid metabolites brain for the cerebrospinal fluid weak organic acid transport system, and it is also possible that saturation of this mechanism may have some importance in the central toxicity of Salicylates.

Abstract

A weak organic acid transport system, similar to that in kidney, has been demonstrated in the cerebrospinal fluid. The putative locus of this transport system is the choroid plexus. In the present study salicylic acid transport by this system was investigated. Rabbit and eat Choroid plexuses were ineubated from 5 to 60 minutes in artificial cerebrospinal fluid containing 3 H-salieylic acid and 14 C-inulin. Rabbit and, to a lesser extent, cat choroid plexus concentrated salieylic acid against a gradient, the tissue/medium ratio after 15 minutes incubation being 11.0 for rabbit and 3.2 for the cat. Uptake of salicylate could be reduced by : 1) increasing the salicylate concentration, 2) reducing temperature, 3) omitting glucose or oxygen or 4) adding para -aminohippuric acid or iodopyracet to the medium. Kinetic analysis revealed that salicylate was transported into the choroid plexus by a process with a nonsaturable and saturable component, the latter satisfying Michaelis-Menton kinetics. A Lineweaver-Burk transfornmation of the transport values for the saturable component yielded a K t of 0.96 mM and a V max Of 86.5 mµmol/ml/min. Thus, in vivo , it is possible that salicylate may compete with therapeutically important drugs and acid metabolites brain for the cerebrospinal fluid weak organic acid transport system. Moreover, it is also possible that saturation of this mechanism may have some importance in the central toxicity of salicylates.