S11.3 Mechanism of gastric vagal modulation by umami

Abstracts / Autonomic Neuroscience: Basic and Clinical 149 (2009) 1–126

coupled receptors and associated the G proteins shown to mediate taste modalities in the lingual epithelium. Gut endocrine cells may also be able to detect the presence of microbes, via expression of bacterial recognition receptors such as toll-like receptors, or receptors for bacterial products, such as short chain fatty acids. Given the diversity of molecules that are detected at the luminal surface of gut endocrine cells and the effects on food intake and plasma glucose, make these cells attractive targets for the development of specific molecules that may be useful for body weight regulation and improved glucose homeostasis. doi:10.1016/j.autneu.2009.05.056

S11.2 Role of gustducin, taste receptors and transient receptor potential channel M5 in gastrointestinal chemosensation B. Mosinger, Z. Kokrashvili, R.F. Margolskee (Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA) Taste receptors, gustducin, the transient receptor potential channel M5 (Trpm5) and other taste proteins are expressed in multiple types of gut cells. Human enteroendocrine L cells express GLP-1 along with many taste proteins. Mouse L cells also express gustducin, and gustducin knockout mice have deficiencies in secretion of GLP-1, and in regulation of plasma insulin and blood glucose. Isolated small intestine and intestinal villi from gustducin null mice display defective GLP-1 secretion in response to glucose. GLP-1 release from L cell lines is promoted by sugars and sweeteners, and blocked by the sweet receptor antagonist lactisole or siRNA to gustducin. Thus, L cell-expressed gustducin and sweet receptor are implicated in sugar sensing in gut. Other cells in mouse duodenum (a subset of brush cells) express Trpm5, beta-endorphin and Metenkephalin. Wildtype mice secrete beta-endorphin into the gut lumen in response to high osmolarity stimuli. However, stimulated secretion of opioids is markedly attenuated in Trpm5 null mice. Trpm5-expressing brush cells of gut have chemosensory properties and appear to be a type of solitary chemosensory cell (SCC). We infer that brush cell-expressed Trpm5 is required for secretion of betaendorphin into the intestinal lumen in response to feeding. Acknowledgments: Supported by NIH grants DC007399 and DK073248 to BM and DC03055 and DC03155 to RFM.

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study we investigated the effects of intraluminal MSG at concentrations, which induce umami sensation orally, on single gastric vagal afferent fibers to characterize MSG-responsive afferent fiber types as well as change on gastric contractions in urethane-anesthetized rats. Electrophysiological recording of afferent activity in finely dissected bundles of the distal branch of the ventral gastric vagus nerve (VGV) with concomitant intragastric manometry were performed in pylorusligated urethane-anesthetized male SD rats. Consecutive gastric stimulation (20 min per trial, 10 min intertrial intervals) with 1.5– 2 ml of isotonic (150 mM) solutions containing 0, 30, 60, 150 mM MSG was applied intraluminally. Of eighteen single unit records sorted from multi-unit afferent recordings in five experiments, 3/18 fibers (17%) exhibited clear dose-related increases in discharge with increasing intraluminal MSG. These fibers had low initial ongoing discharge rates (0.64 ± 0.25 Hz). Excluding the immediate phasic response to gastric distention present in 2/3 of these fibers, peak excitation (140 ± 52% increase relative to saline) occurred 6.3 ± 0.9 min after the start of intraluminal infusion of 150 mM MSG. Additionally, four units with either low irregular ongoing activity or intermittent rare clustered activity responded with elevated bursting activity during intraluminal stimulation with 60 or 150 mM MSG, but not both. Of the seven units activated differentially during MSG stimulation, six were tested with iv CCK-8 (0.3 µg/kg), and four (67%) responded, while excitation by 5-HT (10 µg/kg iv) was observed in 3/4 units tested. MSG had a tendency to lower intragastric pressure after intragastric infusion, but had no significant effect on gastric motility indexes. In conclusion, intraluminal glutamate excites a subset of chemoresponsive gastric vagal afferent units having low or intermittent spontaneous activity and lacking tonic mechanoresponsiveness, with varying patterns of glutamate-induced excitation. The data suggest a potentially wide diversity of vagal afferent chemoreceptive units, consistent with the variety of potential stimulants of gastric taste receptors. Umamiactivated vagal afferent signals may contribute other gastric functions such as gastric secretion [3] than contractions through the gastric vagal–vagal reflex. [1] San Gabriel, A.M., 2007. mGluR1 in the fundic glands of rat stomach. FEBS Lett 581, 1119–23. [2] Uneyama, H., 2006. Luminal amino acid sensing in the rat gastric mucosa. Am. J. Physiol. 291,G1163–70. [3] Zolotarev, V., Effect of free dietary glutamate on gastric secretion in dogs. Annals NY Acad. Sci. in press. doi:10.1016/j.autneu.2009.05.058

doi:10.1016/j.autneu.2009.05.057 S11.4 Mechanisms of forebrain neural response to the gut nutrients in rats S11.3 Mechanism of gastric vagal modulation by umami T. Tanaka, D.W. Adelson, H.P. Kosoyan, Y. Taché (CURE:DDRC and CNS and Women's Health, VAGLAHS and UCLA David Geffen School of Medicine, Los Angeles, CA 90403, USA) L-glutamate acts on mGluR1 and T1r1 + 3 receptors in taste buds to stimulate umami sensation, one of the five basic taste qualities. Recently, mGluR1 and T1r1 + 3 also have been found in the gastric antrum of the rat, particularly in the fundic glands [1]. Since gastric mucosal pepsinogen expression is increased by a diet supplemented with 1% glutamate, it has been suggested that a gastric umami signaling pathway may influence gastric phase regulation of protein digestion, in part via vagal pathways. Intraluminal monosodium glutamate (MSG) has a slow-onset excitatory effect on mass vagal afferent activity mainly through 5-HT3 receptor activation [2], but the afferent fibers responsible at the single-unit level or its effect on gastric contraction, one of vagal outputs, have not been studied to date. In this

T. Tsurugizawa, A. Uematsu, H. Uneyama, K. Torii (Institute of Life Sciences, Ajinomoto Co., Inc., Kawasaki, Japan) Recent studies have shown the expression of nutrient-sensing systems transmitting nutritive information from the gastrointestinal tract to the brain [1]. We have already shown that intragastric infusion of l-glutamate or glucose elicits the neural activity in the rat forebrain. It still remained, however, which pathway is a main pathway to transmit the nutrient information from the gut to the brain; vagus nerve or circulation. In this presentation, using functional magnetic resonance imaging (fMRI), we will provide the evidence that vagus nerve is one of the main pathway to convey the gut l-glutamate information and insulin rather than blood glucose is one of the main hormones to convey the information of glucose [2]. Rats were anesthetized with alpha-chloralose and after 30 min MRI scanning was started. Thirty min after the start of scanning, 60 mM monosodium l-glutamate (MSG) and glucose solution was infused into