Kunihiko Higashiura

γ-Glutamyltaurine has potent and long-lasting antiepileptic action as demonstrated by intra-amygdaloid injection in amygdala-kindled rats

Intra-amygdaloid injections of gamma-glutamyltaurine, a recently identified brain dipeptide, strongly suppressed seizures in amygdala-kindled rats stimulated with intensities 10 or 50 microA above the generalized seizure triggering threshold (mean 82 microA). The suppressive effect persisted as long as 3 days. Taurine had relatively weak suppressive effects. Thus gamma-glutamyltaurine seems much more potent than taurine in the suppression of epileptic seizures when injected directly into the kindling site.

Effects of intraamygdaloid injection of taurine and valyltaurine on amygdaloid kindled seizure in rats.

Abstract: Antiepileptic effects of intracerebral injections of taurine and valyltaurine were examined in amygdaloid kindled rats. The effects were assessed whether the animals can evoke generalized seizures by a 10,μA higher stimulation intensity than triggering thresholds. In all fully‐kindled animals that have received intraamygdaloid injection of 500 nmol taurine, the kindled seizure was completely abolished. Such a significant seizure suppression (p < 0.05) was observed 12–24 h after the taurine injection. Valyltaurine (500 nmol) also suppressed the seizure in 60% of animals tested, but the effect was not statistically significant. The results indicate that taurine may effectively suppress epileptic seizures when it acts directly at the stimulation site amygdala.

Isolation of Glutamyltaurine from Bovine Brains and Proof of Its γ‐Linkage by the B/E Linked Scan SIMS Technique

Abstract: We isolated a glutamyltaurine from bovine brains and determined its structure as γ‐glutamyltaurine (γ‐Glu‐Tau; glutaurine) by use of a new mass spectrometric technique [B/E linked scan sputtered ion mass spectrometry (SIMS)], which we have recently shown to be useful for distinguishing the γ‐ from the α‐isomer of glutamyl‐dipeptides. Neither the α‐isomer of glutamyltaurine nor any aspartyltaurines could be detected in bovine brain.

Syntheses and properties of optically active 2-substituted taurines

The synthesis of nine 2-substituted taurines (5a–i), including the marine natural product D-cysteinolic acid (5f), are described. These involve the successive conversion of N-t-butoxycarbonyl(Boc)-protected amino acid esters (1) into the N-Boc-2-aminoethanols (2), their O-mesylated derivatives (3), the deprotected 2-aminoethyl methanesulphonates (4), followed by the replacement of the mesyloxy group by a sulpho group to give the optically active taurines (5a–e,g–i). Hydrogenolysis of 2-benzyloxymethyltaurine (5e) gives D-cysteinolic acid (5f). The structure of another of the products, (5b), is also confirmed by an alternative synthesis from N-Boc-valine methyl ester (1b)via two β-bromoethylamine derivatives, (6b) and (7b).

The chemical conversion of C-terminal glycines in peptides into taurine

The first chemical conversion of C-glycine in dipeptides into taurine has been achieved using a general substitution of a sulpho group for a halogeno or mesyl group via the corresponding amino acid 2-halogenoethyl-or 2-methanesulphonyloxyethyl-amides, each of which was prepared from the ethanolamide obtained by LiBH4 reduction of a protected dipeptide containing a C-glycine ester.