Kenji Horie

Dietary γ-aminobutyric acid affects the brain protein synthesis rate in young rats

Summary.The purpose of this study was to determine whether the γ-aminobutyric acid (GABA) affects the rate of brain protein synthesis in male rats. Two experiments were done on five or three groups of young rats (5 wk) given the diets containing 20% casein administrated 0 mg, 25 mg, 50 mg, 100 mg or 200 mg/100 g body weight GABA dissolved in saline by oral gavage for 1 day (d) (Experiment 1), and given the diets contained 0%, 0.25% or 0.5% GABA added to the 20% casein diet (Experiment 2) for 10 d. The plasma concentration of growth hormone (GH) was the highest in rats administrated 50 mg and 100 mg/100 g body weight GABA. The concentration of serum GABA increased significantly with the supplementation groups. The fractional (Ks) rates of protein synthesis in brain regions, liver and gastrocnemius muscle increased significantly with the 20% casein + 0.25% GABA diet and still more 20% casein + 0.5% GABA compared with the 20% casein diet. In brain regions, liver and gastrocnemius muscle, the RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis in any organ. Our results suggest that the treatment of GABA to young male rats are likely to increase the concentrations of plasma GH and the rate of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.

d‐Val22 containing human big endothelin‐1 analog, [d‐Val22]Big ET‐1[16–38], inhibits the endothelin converting enzyme

Endothelin converting enzyme (ECE) is essential for generation of the biological effects of endothelin‐1 (ET‐1) from a precursor, big endothelin‐1 (Big ET‐1). We synthesized four analogs of human Big ET‐1[16–38], substituted with single d‐amino acids at P1, P2, P1′and P2′ positions. ECE activity was determined using an ET‐1 specific radioimmunoassay system. None of the d‐amino acid containing Big ET‐1 analogs were apparently cleaved by ECE, however, one of the synthetic peptides, [d‐Val22]Big ET‐1[16–38], strongly inhibited the ECE activity. Furthermore, when this d‐Val22 containing peptide was preadministrated to rat striatum, it was found to inhibit the dopamine release induced by Big ET‐1. This result suggests that the d‐Val22 containing peptide inhibits the ECE activity in vivo. The d‐Val22 containing inhibitor offers hope of developing more potent and highly specific ECE inhibitors of therapeutic significance.

Endothelin-1 and endothelin-3 modulate dopaminergic neurons through different mechanisms

Novel vasoconstrictor peptides, endothelin-1 (ET-1) and endothelin-3 (ET-3), are also known as neuropeptides or neuromodulators. When either ET-1 or ET-3 was administered to the rat striatum via a microinjection needle, the dopamine release from the striatum dose-dependently increased. Pretreatment with a glutamate receptor blocker, glutamate diethyl ester hydrochloride, inhibited the dopamine release induced by ET-3, whereas it further enhanced the dopamine release by ET-1. This suggests that ET-1 directly induces the dopamine release, whereas the action of ET-3 is mediated by glutamate receptors. We postulate that this difference may result from the different distributions of endothelin receptors: ETA receptors may be present on the dopaminergic neurons, but ETB receptors on the glutamatergic neurons.