TRYPTOPHAN TRANSPORT ACROSS THE SYNAPTOSOMAL MEMBRANE¹

Abstract

Abstract— Crude mitochondrial fractions prepared from rat brains took up l‐tryptophan. The component of the crude mitochondrial fraction responsible for this uptake is the synaptosome. After uptake of tryptophan occurred, rupture of synaptosomes released 97 per cent of the tryptophan unchanged. Rupture of synaptosomes abolished uptake. Penetration of the limiting membrane of synaptosomes by l‐tryptophan both as influx and efflux was studied. Uptake of l‐tryptophan was rapid, temperature dependent, partially inhibited by cyanide, 2‐deoxy‐d‐glucose and ouabain, but apparently unaffected by low external sodium ion concentrations. d‐tryptophan was a poor inhibiteur of l‐tryptophan uptake. Concentration gradients Internal: external of up to 4:1 were achieved. Kinetic studies on l‐tryptophan uptake and its competitive inhibition by l‐phenylalanine indicated a saturable carrier‐mediated transport system, present in the rat at birth. l‐Tryptophan efflux from preloaded synaptosomes was markedly stimulated by certain arrino acids and its influx stimulated by preloading with l‐tryptophan. This countertransport is further evidence for carrier‐mediated or facilitated diffusion. On the basis of countertransport data there seem to be at least two systems for transporting amino acids across synaptosomal membrane. The relevance of these studies to the role of l‐tryptophan as the initial precursor of brain 5‐hydroxytryptamine is examined.

Feedback Regulation of 5‐ht Synthesis in Rat Striatal Slices

“…(GRAHAME-SMITH and PARFITT, 1970;KAROBATH, 1972). Similar conclusions were drawn from in civo studies.…”

A disorder of biogenic amines in dihydropteridine reductase deficiency

“…The present study shows that the defect in biogenic amines is qualitatively different and quantitatively more severe than it is in classic PKU (see Table 3). The neutral aromatic amino acids tyrosine, tryptophan, and phenylalanine have a common transport system across various cell membranes [ 16,401, and in classic PKU decreased absorption of these precursors could result in a fall in blood serotonin and urinary excretion of 5-HIAA [38], a reduction in plasma norepinephrine [34], and diminished urinary excretion of VMA [ 4 ] , dopamine, norepinephrine, and epinephrine [34]. In a study of several adults with untreated classic PKU, levels of HVA and 5-HIAA in lumbar CSF before and after probenecid administration increased following dietary restriction of phenylalanine [29].…”

Effect of p‐chlorophenylalanine on release of 5‐hydroxytryptamine from the rat frontal cortex in vivo

“…The anomalous 5-HTP data are explicable by analogy with the stimulation of tryptophan efflux from synaptosomes by other large neutral amino acids (Grahame-Smith & Parfitt, 1970) since it suggests that as PCPA, like 5-HTP, is a large neutral amino acid it stimulated efflux of the latter into extracellular fluid. As PCPA has a half-life of about 3 days (Koe & Weissman, 1966) its concentration in the brain would still be high at the time of the experiment.…”