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1 CURE, Digestive Diseases Research Center, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, and Molecular Biology Institute, UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: erozengurt{at}mednet.ucla.edu.
Mammalian type 2 taste receptors (T2R) are a family of G- protein coupled receptors (GPCRs) that mediate bitter signals in the taste cells. In the present study, we compared the genomic organization of rodent T2R genes based on recently completed mouse and rat genome and examined tissue and cell-specific expression of T2Rs. Both mouse and rat T2R families consist of 36 intact genes and at least 7 pseudogenes that are mapped to mouse chromosome 15, 2, and 6, and to rat chromosome 2, 3, and 4, respectively. All but two T2R genes are clustered on mouse chromosome 6 and rat chromosome 4 with virtually identical genomic organization. The orthologs of the first human T2R gene identified, mT2R119 and rT2R1 are located on mouse chromosome 15 and rat chromosome 2, while the novel rodent-specific T2R genes, mT2R134 and rT2R34, are located in mouse chromosome 2 and rat chromosome 3, respectively. Our results, using reverse transcriptase-PCR, demonstrate the presence of transcripts corresponding to the putative denatonium benzoate (DB) and phenylthiocarbamide (PTC) receptors in the antrum, fundus and duodenum, as well as in the STC-1 and AR42J cells. The novel rodent-specific T2R gene (mT2R134 and rT2R34) was also expressed in these tissues and cell lines. Addition of DB, PTC or cycloheximide (CYX) to AR42J cells induced a rapid increase in the intracellular Ca2+ concentration. The specificity of these effects is shown by the fact that these bitter stimuli did not induce any detectable Ca2+ signaling in many other rodent or human cells that do not express receptors or G proteins implicated in bitter taste signaling. These results demonstrate that mouse and rat T2R genes are highly conserved in terms of genomic organization and tissue expression, suggesting that rodent T2Rs are evolved under similar dietary pressure and share bitter sensing functions in the lingual and gastrointestinal systems.
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