Brain activation by the umami taste substance monosodium L-glutamate via gustatory and visceral signaling pathways, and its physiological significance due to homeostasis after a meal

AbstractMonosodium l-glutamate (MSG) elicits a unique taste sensation termed umami and is widely used as a flavor enhancer in various cuisines. In addition, recent studies have suggested the existence of receptors for l-glutamate (Glu) and transduction molecules in the gut mucosa as well as in the oral cavity. The gastric afferent vagal nerve responds specifically to luminal stimulation by Glu in the stomach and regulates autonomic reflexes. The intragastric infusion of MSG also activates several brain areas (insular cortex, limbic system, and hypothalamus) and is able to induce flavor-preference learning in rats. These results suggest that Glu signaling via the gustatory and visceral pathways plays an important role in digestion, absorption, metabolism, and other physiological functions by activating the brain

Physiological roles of dietary glutamate signaling via gut–brain axis due to efficient digestion and absorption

Dietary glutamate (Glu) stimulates to evoke the umami taste, one of the five basic tastes, enhancing food palatability. But it is also the main gut energy source for the absorption and metabolism for each nutrient, thus, only a trace amount of Glu reaches the general circulation. Recently, we demonstrated a unique gut sensing system for free Glu (glutamate signaling). Glu is the only nutrient among amino acids, sugars and electrolytes that activates rat gastric vagal afferents from the luminal side specifically via metabotropic Glu receptors type 1 on mucosal cells releasing mucin and nitrite mono-oxide (NO), then NO stimulates serotonin (5HT) release at the enterochromaffin cell. Finally released 5HT stimulates 5HT(3) receptor at the nerve end of the vagal afferent fiber. Functional magnetic resonance imaging (f-MRI, 4.7 T) analysis revealed that luminal sensing with 1 % (w/v) monosodium l-glutamate (MSG) in rat stomach activates both the medial preoptic area (body temperature controller) and the dorsomedial hypothalamus (basic metabolic regulator), resulting in diet-induced thermogenesis during mealing without changes of appetite for food. Interestingly, rats were forced to eat a high fat and high sugar diet with free access to 1 % (w/w) MSG and water in a choice paradigm and showed the strong preference for the MSG solution and subsequently, they displayed lower fat deposition, weight gain and blood leptin. On the other hand, these brain functional changes by the f-MRI signal after 60 mM MSG intubation into the stomach was abolished in the case of total vagotomized rats, suggesting that luminal glutamate signaling contributes to control digestion and thermogenesis without obesity

豊田法による無カテーテル尿管皮膚痩術の成績

最近9年間に, 43症例67尿管に対し豊田法により無カテーテル尿管皮膚瘻術を行った.対象患者は男性30例, 女性13例, 平均年齢は61.4歳で, そのほとんどが膀胱, 直腸, 前立腺, 子宮の悪性腫瘍であった.両側性の場合は, 原則として左右尿管を一ヵ所に出す二連銃式尿管皮膚吻合術(double barrel ureterostomy)を行った.術前術後の腎盂像の推移をIVPで追求できた60尿管についてみると, 単側性の場合は20尿管中4尿管を除けばほぼ満足すべき結果を得ている.Double barrel法40尿管について, stoma側では中等度以上の腎盂拡張が20尿管中3尿管であったが, stomaと反対側では腎機能に影響が出ることが多く, 20尿管中3尿管に中等度の腎盂拡張が, また5尿管に高度の腎盂拡張または腎機能喪失があった.術後間もなく汎血管内凝固症候群で死亡した1例を除き, 結果的にはstoma付近が強い炎症性肉芽に覆われた1例と尿管の狭窄を生じた2例を除いた42例中39例(92.8%)をtubelessの尿管皮膚瘻としえたTubeless cutaneous ureterostomy by Toyoda's method was conducted in 67 ureters from 43 patients during the last 9 years. Subjects included 30 males and 13 females, with an average age of 61.4 years. Most of them were afflicted with malignant tumors in the bladder, rectum, prostate, or uterus. For bilateral ureterostomy, the double-barrel method was performed in which the stoma was made at the same site in both the right and left ureters. Among 60 ureters in which pre- and postoperative changes in the renal pelvis could be traced by IVP, satisfactory results were obtained in 16 of 20 ureters treated by unilateral surgery. Of the 40 ureters treated by the double-barrel method, moderate or severe pyeloectasis was observed in 3 of the 20 ureters on the side of the stoma, while moderate pyeloectasis was seen in 3 of 20 ureters of the side opposite the stoma, and severe pyeloectasis or loss of renal function was noted in 5. Thus, renal function on the side opposite the stoma was frequently influenced by the procedure. A patient who died of disseminated intravascular coagulation syndrome soon after the operation was excluded from analysis. Tubeless cutaneous ureterostomy could be conducted in 39 of 42 patients (92.8%), excluding one whose stoma and its periphery were covered with severe inflammatory granulation and 2 with ureteral constriction

Formation of Galactic Center Magnetic Loops

A survey for the molecular clouds in the Galaxy with NANTEN mm telescope has discovered molecular loops in the Galactic center region. The loops show monotonic gradients of the line of sight velocity along the loops and the large velocity dispersions towards their foot points. It is suggested that these loops are explained in terms of the buoyant rise of magnetic loops due to the Parker instability. We have carried out global three-dimensional magneto-hydrodynamic simulations of the gas disk in the Galactic center. The gravitational potential is approximated by the axisymmetric potential proposed by Miyamoto & Nagai (1975). At the initial state, we assume a warm (~ 10^4 K) gas torus threaded by azimuthal magnetic fields. Self-gravity and radiative cooling of the gas are ignored. We found that buoyantly rising magnetic loops are formed above the differentially rotating, magnetically turbulent disk. By analyzing the results of global MHD simulations, we have identified individual loops, about 180 in the upper half of the disk, and studied their statistical properties such as their length, width, height, and velocity distributions along the loops. Typical length and height of a loop are 1kpc and 200pc, respectively. The line of sight velocity changes linearly along a loop and shows large dispersions around the foot-points. Numerical results indicate that loops emerge preferentially from the region where magnetic pressure is large. We argue that these properties are consistent with those of the molecular loops discovered by NANTEN.Comment: 16pages, 10figures. Accepted for publication in PASJ. Replace to higher resolution versio

Lysine and Arginine Reduce the Effects of Cerebral Ischemic Insults and Inhibit Glutamate-Induced Neuronal Activity in Rats

Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid), arginine, and their combination on ischemic insults (cerebral edema and infarction) and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed 2 days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg), arginine (0.6 g/kg), or their combined administration (0.6 g/kg each). Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg), were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal) applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction), especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects

Dietary monosodium glutamate enhances gastric secretion

Dietary L-glutamate (Glu), an amino acid abundant in many foodstuffs in a free form, is able to modulate physiological functions in the stomach, including secretion and motility. Recently, specific receptors for Glu were identified in the apical membrane of chief cells in the lower region of fundic glands and in the somatostatin-secreting D-cell fraction of the gastric mucosa. This Glu-sensing system in the stomach is linked to activation of the vagal afferents. Among 20 kinds of amino acid, luminal Glu alone activated the vagal afferents in the stomach through a paracrine cascade led by nitric oxide and followed by serotonin (5-HT). In dogs with Pavlov pouches, found that supplementation of an amino acid-rich diet lacking Glu with monosodium Glu (MSG) enhanced the secretion of acid, pepsinogen, and fluid. However, MSG did not affect these secretions induced by a carbohydrate-rich diet and it had no effect on basal secretion when MSG was applied alone without the diet. Enhancement of gastric secretion by MSG was abolished by blockage of the gastric afferents using intra-gastric applied lidocaine. This effect of MSG was due in part to stimulation of 5-HT3 receptors in the gastric mucosa

Taste, visceral information and exocrine reflexes with glutamate through umami receptors

Chemical substances of foods drive the cognitive recognition of taste with the subsequent regulation of digestion in the gastrointestinal (GI) tract. Tastants like glutamate can bind to taste membrane receptors on the tip of specialized taste cells eliciting umami taste. In chemical-sensing cells diffused through the GI tract, glutamate induces functional changes. Most of the taste-like receptor-expressing cells from the stomach and intestine are neuroendocrine cells. The signaling molecules produced by these neuroendocrine cells either activate afferent nerve endings or release peptide hormones that can regulate neighboring cells in a paracrine fashion or travel through blood to their target receptor. Once afferent sensory fibers transfer the chemical information of the GI content to the central nervous system (CNS) facilitating the gut-brain signaling, the CNS regulates the GI through efferent cholinergic and noradrenergic fibers. Thus, this is a twoway extrinsic communication process. Glutamate within the lumen of the stomach stimulates afferent fibers and increases acid and pepsinogen release ; whereas on the duodenum, glutamate increases the production of mucous to protect the mucosa against the incoming gastric acid. The effects of glutamate are believed to be mediated by G proteincoupled receptors expressed at the lumen of GI cells. The specific cell-type and molecular function of each of these receptors are not completely known. Here we will examine some of the glutamate receptors and their already understood role on GI function regulation

Contribution of umami taste substances in human salivation during meal

The oral gustatory perception during a meal has very important physiological roles such as inducing appetite, smoothing mastication and swallowing, promoting digestion and each nutrient availability. One hundred years ago, L-glutamate was discovered as a new taste substance in Japan. Since then, Japanese taste physiologists have lead the research to establish L-glutamate as the prototype molecule for the fifth basic taste (umami taste), in addition to saltiness, sweetness, bitterness and sourness. Meanwhile, various lines of evidence demonstrated that taste perception is linked to taste stimulioral/ pharyngeal reflexes. In this review, we focus on the efficacy of L-glutamate for human salivation and discuss the possible application of umami taste simulation to the nutritional management for the elderly due to amelioration of their quality of life (QOL)

Discovery of Molecular Loop 3 in the Galactic Center: Evidence for a Positive-Velocity Magnetically Floated Loop towards L=355∘−359∘L=355^\circ-359^\circ

We have discovered a molecular dome-like feature towards $355^{\circ} \leq l \leq 359^{\circ}$ and $0^{\circ} \leq b \leq 2^{\circ}$. The large velocity dispersions of 50--100 km s$^{-1}$ of this feature are much larger than those in the Galactic disk and indicate that the feature is located in the Galactic center, probably within $\sim1$ kpc of Sgr A$^{*}$. The distribution has a projected length of $\sim600$ pc and height of $\sim300$ pc from the Galactic disk and shows a large-scale monotonic velocity gradient of $\sim130$ km s $^{-1}$ per $\sim600$ pc. The feature is also associated with HI gas having a more continuous spatial and velocity distribution than that of $^{12}$CO. We interpret the feature as a magnetically floated loop similar to loops 1 and 2 and name it "loop 3". Loop 3 is similar to loops 1 and 2 in its height and length but is different from loops 1 and 2 in that the inner part of loop 3 is filled with molecular emission. We have identified two foot points at the both ends of loop 3. HI, $^{12}$CO and $^{13}$CO datasets were used to estimate the total mass and kinetic energy of loop 3 to be \sim3.0 \times 10^{6} \Mo and $\sim1.7 \times 10^{52}$ ergs. The huge size, velocity dispersions and energy are consistent with the magnetic origin the Parker instability as in case of loops 1 and 2 but is difficult to be explained by multiple stellar explosions. We argue that loop 3 is in an earlier evolutionary phase than loops 1 and 2 based on the inner-filled morphology and the relative weakness of the foot points. This discovery indicates that the western part of the nuclear gas disk of $\sim1$ kpc radius is dominated by the three well-developed magnetically floated loops and suggests that the dynamics of the nuclear gas disk is strongly affected by the magnetic instabilities.Comment: 30 pages, 10 figures. High resolution figures are available at http://www.a.phys.nagoya-u.ac.jp/~motosuji/fujishita09_figs

A Detailed Observational Study of Molecular Loops 1 and 2 in the Galactic Center

Fukui et al. (2006) discovered two huge molecular loops in the Galactic center located in (l, b) ~ (355 deg-359 deg, 0 deg-2 deg) in a large velocity range of -180-40 km s^-1. Following the discovery, we present detailed observational properties of the two loops based on NANTEN 12CO(J=1-0) and 13CO(J=1-0) datasets at 10 pc resolution including a complete set of velocity channel distributions and comparisons with HI and dust emissions as well as with the other broad molecular features. We find new features on smaller scales in the loops including helical distributions in the loop tops and vertical spurs. The loops have counterparts of the HI gas indicating that the loops include atomic gas. The IRAS far infrared emission is also associated with the loops and was used to derive an X-factor of 0.7(+/-0.1){\times}10^20 cm^-2 (K km s^-1)^-1 to convert the 12CO intensity into the total molecular hydrogen column density. From the 12CO, 13CO, H I and dust datasets we estimated the total mass of loops 1 and 2 to be ~1.4 {\times} 106 Msun and ~1.9 {\times} 10^6 Msun, respectively, where the H I mass corresponds to ~10-20% of the total mass and the total kinetic energy of the two loops to be ~10^52 ergs. An analysis of the kinematics of the loops yields that the loops are rotating at ~47 km s-1 and expanding at ~141 km s^-1 at a radius of 670 pc from the center. Fukui et al. (2006) presented a model that the loops are created by the magnetic flotation due to the Parker instability with an estimated magnetic field strength of ~150 {\mu}G. We present comparisons with the recent numerical simulations of the magnetized nuclear disk by Machida et al. (2009) and Takahashi et al. (2009) and show that the theoretical results are in good agreements with the observations. The helical distributions also suggest that some magnetic instability plays a role similarly to the solar helical features.Comment: 40 pages, 22 figures, submitted to publication in PAS