Trpm5 Null Mice Respond to Bitter, Sweet, and Umami Compounds

Damak, Sami; Rong, Minqing; Yasumatsu, Keiko; Kokrashvili, Zaza; Pérez, Cristián A.; Shigemura, Noriatsu; Yoshida, Ryusuke; Mosinger, B; Glendinning, John I.; Ninomiya, Yuzo; Margolskee, Robert F.

doi:10.1093/chemse/bjj027

Cited by 289 publications

(300 citation statements)

References 44 publications

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“…However, the authors also showed that trpm5-/-mice were conditioned to the spatial location of the sipper and not the non-sweet orosensory qualities of sucrose; when trained over repeated sessions with a single sipper, trpm5-/-mice failed to develop a preference for sucrose. This result contrasts with other studies that show trpm5-/-mice are indeed capable of developing a preference for the non-sweet orosensory cues associated with sucrose, as well as other sugars, if given access over 24 h rather than in brief (10-30 min) sessions [64,65]. Thus, different sensory information (visuospatial vs. taste) seems to interact with the reinforcement value of nutrients in distinct ways and the amount of experience with stimuli seems to be an important factor.…”

Section: Genetic Modelscontrasting

confidence: 99%

The role of dopamine in the pursuit of nutritional value

McCutcheon

2015

Physiology & Behavior

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Acquiring enough food to meet energy expenditure is fundamental for all organisms. Thus, mechanisms have evolved to allow foods with high nutritional value to be readily detected, consumed, and remembered. Although taste is often involved in these processes, there is a wealth of evidence supporting the existence of taste-independent nutrient sensing. In particular, post-ingestive mechanisms arising from the arrival of nutrients in the gut are able to drive food intake and behavioural conditioning. The physiological mechanisms underlying these effects are complex but are believed to converge on mesolimbic dopamine signalling to translate post-ingestive sensing of nutrients into reward and reinforcement value. Discerning the role of nutrition is often difficult because food stimulates sensory systems and post-ingestive pathways in concert. Thus, in this mini-review, I discuss the various methods that may be used to study post-ingestive processes in isolation including sham-feeding, nonnutritive sweeteners, post-ingestive infusions, and pharmacological and genetic methods. Using this structure, I present the evidence that dopamine is sensitive to nutritional value of certain foods and examine how this affects learning about food, the role of taste, and the implications for human obesity.

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Section: Genetic Modelscontrasting

confidence: 99%

The role of dopamine in the pursuit of nutritional value

McCutcheon

2015

Physiology & Behavior

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“…TRPM5-GFP and TRPM5 knockout mice (44,45) were bred in-house in University of Colorado at Denver and Health Sciences Center. The PCR was used to genotype the mice based on absence of the deleted coding region of TRPM5 and presence of the neomycin resistance gene.…”

Section: Methodsmentioning

confidence: 99%

Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals

Lin

Margolskee

Donnert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

152

157

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Olfactory sensory neurons (OSNs) in the main olfactory epithelium respond to environmental odorants. Recent studies reveal that these OSNs also respond to semiochemicals such as pheromones and that main olfactory input modulates animal reproduction, but the transduction mechanism for these chemosignals is not fully understood. Previously, we determined that responses to putative pheromones in the main olfactory system were reduced but not eliminated in mice defective for the canonical cAMP transduction pathway, and we suggested, on the basis of pharmacology, an involvement of phospholipase C. In the present study, we find that a downstream signaling component of the phospholipase C pathway, the transient receptor potential channel M5 (TRPM5), is coexpressed with the cyclic nucleotide-gated channel subunit A2 in a subset of mature OSNs. These neurons project axons primarily to the ventral olfactory bulb, where information from urine and other socially relevant signals is processed. We find that these chemosignals activate a subset of glomeruli targeted by TRPM5-expressing OSNs. Our data indicate that TRPM5-expressing OSNs that project axons to glomeruli in the ventral area of the main olfactory bulb are involved in processing of information from semiochemicals.signal transduction ͉ pheromone ͉ stimulated emission depletion (STED) microscopy T he olfactory system perceives not only odorants that convey information on the environment but also semiochemicals (chemicals involved in animal communication, from the Greek semeion for ''sign''), including pheromones (1-4). A key step in transmission of information is activation of the canonical cAMP signaling pathway by binding of odorants to olfactory receptors, resulting in influx of Ca 2ϩ through a cyclic nucleotide-gated (CNG) channel and subsequent depolarization (5, 6). Targeted disruption of elements of the cAMP pathway, including the CNG channel subunit A2 (CNGA2) (7), the G protein G olf (8), or adenylyl cyclase (AC) III (9), result in severe deficit of odorantevoked responses to many odorants, demonstrating the dominant role of the cAMP pathway.Semiochemicals, such as pheromones, social attractants, and major histocompatibility complex (MHC)-related odorants, signal social and sexual status, genetic makeup, and species identity important for the survival of the individual and the species (1, 10-13). Recent studies indicate that both the main olfactory epithelium (MOE) and olfactory bulbs respond to these chemosignals (14, 15). Consistent with these findings, sensory information from the main olfactory bulb projects to areas in the hypothalamus housing neurons that produce gonadotropinreleasing hormone and plays an important role in reproduction (16,17). Further, a class of chemosensory receptors that recognize social amines found in urine have been identified recently in the MOE (18). Thus, it now is clear that the main olfactory system is involved in detection of semiochemicals and that the cAMP signaling pathway plays an important role in signal transduction f...

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“…Taste cells and some gut cells that express TRPM5 also express taste receptors and other elements of the PLCβ2-signaling stream [118,120,125]. Significantly, genetic knockout of TRPM5 renders mice less responsive to sweet, bitter, and umami tastes [120,127].…”

Section: Calcium As a Second Messenger In Tastementioning

confidence: 99%

Signal transduction and information processing in mammalian taste buds

Roper

2007

Pflugers Arch - Eur J Physiol

271

215

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The molecular machinery for chemosensory transduction in taste buds has received considerable attention within the last decade. Consequently, we now know a great deal about sweet, bitter, and umami taste mechanisms and are gaining ground rapidly on salty and sour transduction. Sweet, bitter, and umami tastes are transduced by G-protein-coupled receptors. Salty taste may be transduced by epithelial Na channels similar to those found in renal tissues. Sour transduction appears to be initiated by intracellular acidification acting on acidsensitive membrane proteins. Once a taste signal is generated in a taste cell, the subsequent steps involve secretion of neurotransmitters, including ATP and serotonin. It is now recognized that the cells responding to sweet, bitter, and umami taste stimuli do not possess synapses and instead secrete the neurotransmitter ATP via a novel mechanism not involving conventional vesicular exocytosis. ATP is believed to excite primary sensory afferent fibers that convey gustatory signals to the brain. In contrast, taste cells that do have synapses release serotonin in response to gustatory stimulation. The postsynaptic targets of serotonin have not yet been identified. Finally, ATP secreted from receptor cells also acts on neighboring taste cells to stimulate their release of serotonin. This suggests that there is important information processing and signal coding taking place in the mammalian taste bud after gustatory stimulation.

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Trpm5 Null Mice Respond to Bitter, Sweet, and Umami Compounds

Cited by 289 publications

References 44 publications

The role of dopamine in the pursuit of nutritional value

The role of dopamine in the pursuit of nutritional value

Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals

Signal transduction and information processing in mammalian taste buds

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