Bitter taste receptors

There are some hundred different 7TM receptors involved in perception of bitter tastants. The bitter taste receptors also couple through the G protein gustducin yielding the activated Gag-GTP which can thence activate C.AMP/C.GMP phosphodiesterase, thus lowering cAMP and cGMP concentration. Bitter tastant receptors can also act via pertussis 

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FIGURE 2.3 The three main families of mammalian G-protein-coupled 7TM receptors in mammals. No obvious sequence identity is found between the rhodopsin-like family A, the glucagon/VIP/calcitonin family B, and the metabotropic glutamate/chemosensor family C of G-protein-coupled 7TM receptors, with the exception of the disulfide bridge between the top of TM-III and the middle of extracellular loop-2 (see Figure 2.2). Similarly, no apparent sequence identity exists among members of these three families and, for example the 7TM bitter taste receptors, the V1R pheromone receptors, and the 7TM frizzled proteins, which all are either known or believed to be G-protein-coupled receptors. Bacteriorhodopsins, which are not G-protein-coupled proteins but proton pumps, are totally different in respect to amino-acid sequence but have a seven-helical bundle arranged rather similarly to that for the G-protein-coupled receptors. 

Insect chemosensory organs have been differentially developed for taste and olfactory sensing. The contact and the distant chemosensory sensilla are responsible for nonvolatile and volatile chemical reception, respectively. The CHCs with long carbon chains are non-volatile, and therefore thought to be received by taste sensilla (Ebbs and Amrein, 2007). However, because of their insolubility in water, it was very difficult to obtain response recordings to them from taste sensilla. Success was recently obtained, however, in Drosophila melanogaster, where a male-specific CHC as a sex-pheromone inhibiting male-male courtship was found to stimulate the bitter taste receptor neuron within the... 

In order to make precise kinetic measurements of the relationship between the strength of stimulus and the magnitude of response in each receptor neuron, it is necessary to use adequate stimuli for the targeting receptor neuron. For example, a taste sensillum of flies houses four functionally differentiated chemoreceptor neurons corresponding to insect fundamental tastes sugar, salt, water and bitter taste receptor neurons. These four receptor neurons, when stimulated by adequate stimuli, generate distinguishable impulses by their... 

Thus, using these techniques, it has been suggested that a sex-pheromone CHC of Drosophila stimulates the bitter taste receptor neuron in a CHC concentration-dependent manner. Moreover, the cross adaptation test between the sex-pheromone CHC and an ordinary bitter substance supported the idea that the sex-pheromone CHC tastes bitter (Lacaille el al., 2007). 

Intensive studies on the bitter taste receptor are also in progress, as with the sweet taste receptor.119 In fact, it has been reported that T2R receptors are necessary and sufficient for the detection and perception of bitter... 

Table 1 List of deorphanized mammalian bitter taste receptors with their cognate agonists...

Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ. T2Rs function as bitter taste receptors. Cell 2000 100 703-711. 

Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W. Members of RTP and REEP gene families influence functional bitter taste receptor expression. J. Biol. Chem. 2006 281 20650-20659. 

Behrens M, Meyerhof W. Bitter taste receptors and human bitter taste perception. Cell. Mol. Life Sci. 2006 63 1501-1509. 

Sainz E, Cavenagh MM, Gutierrez J, Battey JF, Northup JK, Sullivan SL. Functional characterization of human bitter taste receptors. Biochem. J. 2007 403 537-543. 

Kuhn C, Bufe B, Winnig M, Hofmann T, Frank O, Behrens M, Lewtschenko T, Slack IP, Ward CD, Meyerhof W. Bitter taste receptors for saccharin and acesulfame K. J. Neurosci. 2004 24 10260-10265. 

Floriano WB, Hall S, Vaidehi N, Kim U, Drayna D, Goddard WA 3rd. Modeling the human PTC bitter-taste receptor interactions with bitter tastants. J. Mol. Model. 2006 12 931-941. 

Miguet L, Zhang Z, Grigorov MG. Computational studies of ligand-receptor interactions in bitter taste receptors. J. Recept. Signal. Transduct. Res. 2006 26 611-630. 

Go Y. Proceedings of the SMBE Tri-National Young Investigators Workshop Lineage-specific expansions and contractions of the bitter taste receptor gene repertoire in vertebrates. Mol. Biol. Evol. 2006 23 964-972. 

Fischer A, Gilad Y, Man O, Paabo S. Evolution of bitter taste receptors in humans and apes. Mol. Biol. Evol. 2005 22 432-436. Go Y, Satta Y, Takenaka O, Takahata N. Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates. Genetics 2005 170 313-326. 

Wang X, Thomas SD, Zhang 1. Relaxation of selective constraint 91. and loss of function in the evolution of human bitter taste receptor genes. Hum. Mol. Genet. 2004 13 2671-2678. 

Shi P, Zhang 1, Yang H, Zhang YP. Adaptive diversification of 93. bitter taste receptor genes in Mammahan evolution. Mol. Biol. 

Soranzo N, Bufe B, Sabeti PC, Wilson IF, Weale ME, Mar- 94. guerie R, Meyerhof W, Goldstein DB. Positive selection on a high-sensitivity allele of the human bitter-taste receptor TAS2R16. 

Wooding S, Kim UK, Bamshad Ml, Larsen J, Jorde LB, Drayna D. 96. Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. Am. J. Hum. Genet. 2004 74 637-646. 

Wu SV, Rozengurt N, Yang M, Young SH, Sinnett- Smith J, Rozengurt E. Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc. Natl. Acad. Sci. U. S. A. 2002 99 2392-2397. 

Figure 32.15. Evidence that T2R Proteins Are Bitter Taste Receptors. Cycloheximide uniquely stimulates the...

Figure 32.16. Differing Gene Expression and Connection Patterns in Olfactory and Bitter Taste Receptors. In...

Kim UK, Wooding S, Ricci D, Jorde LB, Drayna D (2005) Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci. Hum Mutat 26 199-204 Kim UK, Wooding S, Riaz N, Jorde LB, Drayna D (2006) Variation in the human TAS1R taste receptor genes. Chem Senses 31 599-611... 

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