Contribution of α-Gustducin to Taste-guided Licking Responses of Mice

Chemical Senses, May 2005

Glendinning, John I., Bloom, Lauren D., Onishi, Maika, Zheng, Kun Hao, Damak, Sami, Margolskee, Robert F., Spector, Alan C.

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Contribution of α-Gustducin to Taste-guided Licking Responses of Mice

Advance Access publication March Contribution of a-Gustducin to Taste-guided Licking Responses of Mice John I. Glendinning 2 3 Lauren D. Bloom 2 3 Maika Onishi 2 3 Kun Hao Zheng 2 3 Sami Damak 1 2 Robert F. Margolskee 0 1 2 Alan C. Spector 2 4 0 Howard Hughes Medical Institute 1 Department of Physiology and Biophysics, Mount Sinai College of Medicine 2 3009 Broadway , New York, NY 10027 , USA 3 Department of Biological Sciences, Barnard College, Columbia University 4 Department of Psychology, University of Florida , USA We examined the necessity of a-gustducin, a G protein a-subunit expressed in taste cells, to taste-mediated licking responses of mice to sapid stimuli. To this end, we measured licking responses of a-gustducin knock-out (Gus / ) mice and heterozygotic littermate controls (Gus+/ ) to a variety of bitter , umami , sweet , salty and sour taste stimuli. All previous studies of how Gus / mice ingest taste stimuli have used long-term (i.e. 48 h) preference tests, which may be confounded by post-ingestive and/or experiential effects of the taste stimuli. We minimized these confounds by using a brief-access taste test, which quantifies immediate lick responses to extremely small volumes of sapid solutions. We found that deleting a-gustducin (i) dramatically reduced the aversiveness of a diverse range of bitter taste stimuli; (ii) moderately decreased appetitive licking to low and intermediate concentrations of an umami taste stimulus (monosodium glutamate in the presence of 100 lM amiloride), but virtually eliminated the normal aversion to high concentrations of the same taste stimulus; (iii) slightly decreased appetitive licking to sweet taste stimuli; and (iv) modestly reduced the aversiveness of high, but not low or intermediate, concentrations of NaCl. There was no significant effect of deleting a-gustducin on licking responses to NH4Cl or HCl. taste; a-gustducin; brief-access taste test; knock-out mice Introduction In mammals, the ingestive response to sweeteners, amino acids and many bitter compounds is initiated by the interaction of chemical compounds with G-protein-coupled receptors (GPCRs) on the apical membrane of taste cells (Gilbertson et al., 2000; Glendinning et al., 2000) . Two families of GPCRs are known to mediate this detection process—the T2Rs and T1Rs. A few T2Rs have been shown to respond selectively to compounds that elicit bitter taste sensations in humans (Adler et al., 2000; Chandrashekar et al., 2000; Bufe et al., 2002) . The T1Rs, which appear to function predominantly as heterodimers, are activated by amino acids and sweeteners (natural and artificial). The heterodimer of T1R2+T1R3 responds selectively to compounds that elicit sweet taste sensations in humans, whereas that of T1R1+T1R3 responds selectively to compounds that elicit umami taste sensations (Nelson et al., 2001; Zhao et al., 2003) . Once these taste receptors are activated by their respective ligands, they activate one or more G-proteins (gustducin, rod-transducin or Gi2), which in turn stimulate one or more effector systems (adenylyl cyclase, phosphodiesterase or phospholipase C b2; Huang et al., 1999; Clapp et al., 2001; Yan et al., 2001; Ogura et al., 2002) . These early transduction steps initiate a cascade of downstream events, including the release of neurotransmitter from the taste cell, generation of action potentials in the postsynaptic afferent neuron, propagation of the action potentials up the gustatory neuraxis, and, ultimately, ingestion or rejection Glendinning et al., 2000; Spector, 2000). There is compelling evidence that the a-subunit of gustducin (a-gustducin) contributes significantly to the transduction of bitter , sweet and umami taste stimuli (Wong et al., 1996; Ruiz-Avila et al., 2001; He et al., 2002, 2004; Ruiz et al., 2003) . Gustducin is co-expressed with T1Rs or T2Rs in some taste cells (Adler et al., 2000; Max et al., 2001; Li et al., 2002; Kim et al., 2003) and its subunits have been shown to activate specific components of known gustatory effector systems (e.g. PLC-b2, PDE and Ca2+ store-operated channels) in signaling pathways responsive to sweet and bitter compounds (Huang et al., 1999; Clapp et al., 2001; Yan et al., 2001; Ogura et al., 2002) . a-Gustducin knockout mice (i.e. Gus / mice) exhibit diminished behavioral and/or gustatory nerve responsiveness to natural and artificial sweeteners (Wong et al., 1996; He et al., 2002) , bitter compounds (Ruiz-Avila et al., 2001; Wong et al., 1996; He et al., 2002; Caicedo et al., 2003; Ruiz et al., 2003) and amino acids (Ruiz et al., 2003; He et al., 2004) . Transgenic expression of wild-type a-gustducin in Gus / mice restores normal behavioral responsiveness to these taste stimuli (Ruiz-Avila et al., 2001). While there is no doubt that a-gustducin contributes to the transduction of sweet , bitter and umami taste stimuli, the following observations indicate that other G proteins are also involved in thes (...truncated)


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Glendinning, John I., Bloom, Lauren D., Onishi, Maika, Zheng, Kun Hao, Damak, Sami, Margolskee, Robert F., Spector, Alan C.. Contribution of α-Gustducin to Taste-guided Licking Responses of Mice, Chemical Senses, 2005, pp. 299-316, Volume 30, Issue 4, DOI: 10.1093/chemse/bji025