The transport of L-tryptophan from cerebrospinal fluid in the dog

1. Endogenous tryptophan is uniformly distributed in dog cerebrospinal fluid (c.s.f.) and is about one tenth of the normal fasting plasma level.2. Using a recirculatory ventriculo-cisternal perfusion technique in conscious dogs it was found that L-tryptophan was removed from c.s.f. by a non-saturable mechanism in addition to bulk absorption of c.s.f. The clearance of L-tryptophan from c.s.f. was unaffected by thiopentone anaesthesia.3. Dialysis of dog plasma against an artificial c.s.f. solution containing L-tryptophan demonstrated that a large proportion of the tryptophan in dog plasma was protein-bound and that the unbound diffusible proportion would equilibrate with tryptophan concentrations equivalent to those normally found in dog c.s.f.4. Use of an open-circuit ventriculo-cisternal perfusion system in unanaesthetized dogs revealed the presence of a saturable component in the transport of tryptophan from c.s.f.5. As [(14)C]L-tryptophan infused into a recirculatory perfusion system produced no radioactively labelled metabolites, it was concluded that removal of tryptophan from c.s.f. by cerebral metabolism does not contribute substantially to maintaining the low levels of tryptophan in c.s.f. but that brain uptake associated with protein-binding may give rise to a small saturable component. The results indicate that the actual concentration gradient of tryptophan between plasma and c.s.f. is much less than it appears from the total concentration of tryptophan in the two fluids, and that the mechanism by which the c.s.f. - plasma distribution of tryptophan is maintained is mainly attributable to simple diffusion.