Introduction to the symposium

This issue of the Journal contains the proceedings of a symposium, held in Tokyo, Japan, 11–13 September 2008, to honor the discovery a century ago by Kikunae Ikeda, a physical chemist at Tokyo Imperial University, of the active taste principle in a seaweed favored by the Japanese in cooking. The structure of this tastant turned out to be simple, the sodium salt of glutamic acid (monosodium glutamate; MSG). This taste was termed umami (a Japanese word) and is similar to the taste described in English as ‘‘meaty’’ or ‘‘savory.’’ Umami is found as a dominant taste in ripe tomatoes and ripened cheeses such as parmesan. Hence, a pasta meat sauce sprinkled with parmesan or pizza represent clear examples of the umami taste in Western cuisines. It has been just a decade since the International Glutamate Technical Committee (IGTC) last sponsored a major symposium on glutamate (1), which normally might be considered a rather short period of time, given that glutamate might not be expected to be the focus of fervent research activity. The interval between the first and second symposia was 20 y (2). But, as the organizing committee proceeded to construct the 2008 symposium, it quickly became apparent that a robust area of research had budded and flowered in the decade since the last symposium, focused largely on umami taste. The most parsimonious explanation for the increased pace of research is that, since the last symposium, molecular biology intersected with taste biology, with remarkable consequences (3–5). Whereas the notion of taste glutamate (GLU) receptors was in evidence at the last IGTC symposium, data were few, and the molecular biology effort had not begun. The present symposium and proceedings reflect the explosion of taste studies and data since Ikeda’s seminal work. Early studies that led to the demonstration of a specific taste for MSG (umami), based on psychophysical and electrophysiologic approaches, are discussed first (6, 7). Then, a series of articles expands on this issue and, through the lens of molecular biology, reveals the multiple taste receptors for MSG, their underlying transduction mechanisms, their responsiveness to various taste molecules, and the hallmark feature of umami taste, the synergism between MSG and nucleotide monophosphates. (As originally identified by Ikeda, MSG is not the only molecule in foods that imparts the umami taste; nucleotide monophosphates not only induce the umami taste but synergize or amplify the umami taste imparted by MSG) (8– 12). Other articles consider the variability of umami taste among animals and humans [a specific ageusia for umami has been identified in humans (13)] and begin to link this variability to mutations in putative umami receptor genes (14–18). Not surprisingly, given the new molecular toolbox, taste investigators also wondered if umami taste receptors might be found outside of the oral cavity, farther down in the gut. This interest was stimulated by earlier work that suggested that luminal GLU stimulated vagal afferent (sensory) fibers (19), which suggested the existence of some type of transduction mechanism. This issue has been taken up by several groups, and as described in several articles, GLU receptors have now been identified in various portions of the stomach and intestines, and potential physiologic functions have begun to be examined (20, 21). It is of interest that a similar approach has also been undertaken for sweet receptors, with remarkable results; this research was also reported in the symposium (22, 23). Although, understandably, the symposium was dominated by excitement over umami receptors, other areas of GLU research were no less interesting. Functional magnetic resonance imaging studies of the human brain response to umami taste were presented, which showed that brain regions that process taste stimuli (primary, secondary, and tertiary taste cortex and related areas) exhibit characteristic increases in activity when umami is tasted, that taste synergism occurs when MSG and nucleotides are applied to the tongue, and that the cortical responses are further enhanced when umami and nucleotides are paired with consonant smells (eg, vegetable) and diminished when subjects are told they are tasting MSG (thus showing cognitive bias at the cellular level) (24, 25). Clearly, the ultimate perception of the umami taste by the brain involves more than just the taste receptors themselves. Other presentations considered the use of MSG in food in attempts to improve the appetite, food intake, and health of elderly subjects (26). Another role for dietary glutamate in gut function that was discussed at the symposium was metabolic, and this discussion focused on recent findings that almost all glutamate consumed in food, free and protein-bound, is used by the gut to generate energy (27, 28). Dietary glutamate is an important energy substrate in this organ (29). Other metabolic aspects of glutamate that were discussed included functions in hepatocytes and b cells (30, 31). Additionally, 2 presentations involved the metabolic handling of glutamate in the brain (32, 33). This latter issue has been of interest from the dietary perspective, because several decades ago, dietary MSG was proposed to enter blood, cross into brain, and adversely affect neuronal communica-