Subchronic tolerance trials of graded oral supplementation with ornithine hydrochloride or citrulline in healthy adults.

Ornithine and citrulline are amino acids used in dietary supplements and nutritional products consumed by healthy consumers, but the safe supplementation levels of these compounds are unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral ornithine (as hydrochloride) and citrulline. Healthy male adults (n = 60, age 41.

Changes in Thyroid Hormone Are Not Involved in Regulating Brain Protein Synthesis in Adults Rats Fed Ornithine.

Brain protein synthesis and the plasma concentration of growth hormone (GH) are sensitive to dietary ornithine. However, dietary ornithine does not increase brain protein synthesis in hypophysectomized rats. Because hypophysectomy may decrease the secretion of thyroid stimulated hormone (TSH), we assessed whether the regulation of brain protein synthesis was mediated by changes in the plasma concentrations of thyroid hormone and ghrelin in the 6-propyl-2-thiouracil (PTU, thyroid inhibitor)-treated or control adult rats fed ornithine.

l-Ornithine and l-lysine stimulate gastrointestinal motility via transient receptor potential vanilloid 1.

Scope: The gastrointestinal (GI) tract senses and responds to intraluminal nutrients and these interactions often affect GI functions. We found that, among basic amino acids, l-ornithine (Orn) and l-lysine (Lys) stimulated but l-arginine (Arg) suppressed GI motility after oral administration (24 mmol/kg) in mice (Orn and Lys, 14.3 and 26.

l-Ornithine stimulates growth hormone release in a manner dependent on the ghrelin system.

We found that intraduodenal administration of l-ornithine (l-Orn) stimulates growth hormone (GH) secretion in Wistar rats, and then investigated its mechanism. GH-releasing activity after intraduodenal administration of l-Orn was blocked by [d-Lys]-GHRP-6, an antagonist of the ghrelin receptor; however, l-Orn (100 μM) has no affinity for the ghrelin receptor, suggesting that the GH-releasing activity of l-Orn is mediated via ghrelin release and activation of the ghrelin receptor. Intraduodenally administered l-Orn increased ghrelin mRNA expression in the duodenum but not in the stomach or hypothalamus.

Comparison of the Effects of Ornithine and Arginine on the Brain Protein Synthesis Rate in Young Rats.

Brain protein synthesis and the plasma concentration of growth hormone (GH) are sensitive to dietary ornithine. The purpose of this study was to determine whether dietary arginine, the metabolite of ornithine, affects the brain protein synthesis, and to that end, the effects of arginine on brain protein synthesis were compared with that of ornithine treatment in young rats. Two experiments were done on five or three groups of young rats (5-wk-old) given 0%, 0.

L-Ornithine intake affects sympathetic nerve outflows and reduces body weight and food intake in rats.

Ingesting the amino acid l-ornithine effectively improves lipid metabolism in humans, although it is unknown whether it affects the activities of autonomic nerves that supply the peripheral organs related to lipid metabolism, such as adipose tissues. Thus, we investigated the effects of l-ornithine ingestion on autonomic nerves that innervate adipose tissues and the feeding behaviors of rats. Intragastric injection of l-ornithine (2.

Effects of time of L-ornithine administration on the diurnal rhythms of plasma growth hormone, melatonin, and corticosterone levels in mice.

The synthesis and secretion of many hormones such as growth hormone (GH), melatonin, and corticosterone, exhibit temporal variations over each day and night. Oral administration of several nutritional factors, including L-ornithine, modulates these hormonal secretions and induces an acute increase in plasma GH levels. However, the impact of L-ornithine on the diurnal rhythms of hormone secretion remains unclear.

Orally administered L-ornithine reduces restraint stress-induced activation of the hypothalamic-pituitary-adrenal axis in mice.

In a previous study, we confirmed that orally administered L-ornithine can be transported into the brain of mice. In addition, orally administered L-ornithine, within a limited dose range, had an anxiolytic-like effect in the elevated plus-maze test. However, the mechanism by which orally administered L-ornithine reduced the stress response in mice is still unclear.

Modulation of the neural glutamate transporter EAAC1 by the addicsin-interacting protein ARL6IP1.

Addicsin (Arl6ip5) is a murine homologue of rat glutamate transporter-associated protein 3-18 (GTRAP3-18), a putative negative modulator of Na+-dependent neural glutamate transporter-excitatory amino acid carrier 1 (EAAC1). Here we report that ADP-ribosylation factor-like 6 interacting protein 1 (Arl6ip1) is a novel addicsin-associated partner that indirectly promotes EAAC1-mediated glutamate transport activity in a protein kinase C activity-dependent manner. Like addicsin, Arl6ip1 is expressed in numerous tissues and proved likely to be co-localized with addicsin in certain neurons in the matured brain.

Neural localization of addicsin in mouse brain.

Addicsin is a member of the prenylated Rab acceptor (PRA) 1 domain family and a murine homolog of the rat glutamate-transporter-associated protein 3-18 (GTRAP3-18). This protein is considered to function as a modulator of the neural glutamate transporter excitatory amino acid carrier 1 (EAAC1). However, its molecular functions remain largely unknown.

Expression profile of addicsin/GTRAP3-18 mRNA in mouse brain.

Addicsin is a murine homologue of rat glutamate-transporter-associated protein 3-18 (GTRAP3-18), a putative modulator of neural glutamate-transporter excitatory amino acid carrier 1 (EAAC1). The other molecular functions of addicsin, however, remain largely unknown. We analyzed here the regional and cellular distribution of addicsin transcript in the mature brain using in situ hybridization analysis, and examined the sequential addicsin mRNA expression levels in the developing brain using Northern blot analysis.

Identification of addicsin/GTRAP3-18 as a chronic morphine-augmented gene in amygdala.

Using subtractive cloning, we identified a 1.4 kb mRNA that was ubiquitously expressed in various tissues; this mRNA was highly up-regulated in amygdala nuclei in mice when morphine was repeatedly administered but not when an opiate-receptor antagonist was co-administered. The mRNA encodes a 23 kDa protein, designated 'addicsin'.