title: Bitter taste receptors: Novel insights into the biochemistry and pharmacology.
abstract: Bitter taste receptors (T2Rs) belong to the super family of G protein-coupled receptors (GPCRs). There are 25 T2Rs expressed in humans, and these interact with a large and diverse group of bitter ligands. T2Rs are expressed in many extra-oral tissues and can perform diverse physiological roles. Structure-function studies led to the identification of similarities and dissimilarities between T2Rs and Class A GPCRs including amino acid conservation and novel motifs. However, the efficacy of most of the T2R ligands is not yet elucidated and the biochemical pharmacology of T2Rs is poorly understood. Recent studies on T2Rs characterized novel ligands including blockers for these receptors that include inverse agonist and antagonists. In this review we discuss the techniques used for elucidating bitter blockers, concept of ligand bias, generic amino acid numbering, the role of cholesterol, and conserved water molecules in the biochemistry and pharmacology of T2Rs.
authors.affiliation: Manitoba Chemosensory Biology (MCSB) Research Group and Department of Oral Biology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada; Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada.
authors.forename: Appalaraju
authors.initials: A
authors.lastname: Jaggupilli
authors.affiliation: Manitoba Chemosensory Biology (MCSB) Research Group and Department of Oral Biology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada.
authors.forename: Ryan
authors.initials: R
authors.lastname: Howard
authors.affiliation: Manitoba Chemosensory Biology (MCSB) Research Group and Department of Oral Biology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada; Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada.
authors.forename: Jasbir D
authors.initials: JD
authors.lastname: Upadhyaya
authors.affiliation: Manitoba Chemosensory Biology (MCSB) Research Group and Department of Oral Biology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada.
authors.forename: Rajinder P
authors.initials: RP
authors.lastname: Bhullar
authors.affiliation: Manitoba Chemosensory Biology (MCSB) Research Group and Department of Oral Biology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada; Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB R3E 0W2, Canada. Electronic address: Prashen.Chelikani@umanitoba.ca.
authors.forename: Prashen
authors.initials: P
authors.lastname: Chelikani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055697:Taste Perception / Q000187:drug effects*
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled
keywords: Bitter blockers; Bitter taste receptors (T2Rs); Cholesterol; Constitutive active mutants; G protein-coupled receptor (GPCR); Ligand bias; Structural water molecules