Abstract
The central nervous system transport and metabolism of salicylate were studied in cats and rabbits. In a previous paper, we demonstrated that, in vitro, the choroid plexus from the cat and the rabbit accumulates salicylate by an active, saturable process. The possibility that such a mechanism also is active in vivo was tested in the present study in which the clearance of salicylate from blood to cerebrospinal fluid (CSF) and from CSF to blood was measured with varying concentrations of salicylate and standard ventriculocisternal perfusion techniques. In other animals, samples of the CSF and tissues were obtained, after intravenous injection of salicylate, to allow calculation of the ratio of salicylate in tissue to salicylate unbound in the plasma at 37°C. These studies showed that salicylate penetrates the CSF of cats and rabbits more readily than do other organic acids. At a concentration of 0.5 µM salicylate it was possible, in the rabbit, to demonstrate minimal, saturable transport from CSF to plasma. This weak active transport system, putatively resident in the choroid plexus, may explain why the ratios of salicylate in CSF to salicylate in plasma at low concentrations of salicylate are somewhat lower than predicted on the basis of passive distribution and pH gradients. These studies demonstrate that the defense of the CSF and indirectly, brain homeostasis, which is so effective in excluding iodide, penicillin and other organic acids as well as certain basic drugs, is relatively ineffective against salicylate.
Footnotes
- Received July 24, 1972.
- Accepted January 22, 1973.
- © 1973 by The Williams & Wilkins Co.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|