摘要:
This invention relates to electrophysiological assays that measure sodium conductance activity of a delta human epithelial sodium channel (ENaC) in the presence and absence of delta hENaC enhancers. Also, the invention generally relates to assays for identifying compounds that enhance the activity of delta hENaC, especially in an oocyte expression system. These compounds have potential application in modulating (enhancing) salty taste perception.
摘要:
This invention relates to electrophysiological assays that measure sodium conductance activity of a delta human epithelial sodium channel (ENaC) in the presence and absence of delta hENaC enhancers. Also, the invention generally relates to assays for identifying compounds that enhance the activity of delta hENaC, especially in an oocyte expression system. These compounds have potential application in modulating (enhancing) salty taste perception.
摘要:
This invention relates to novel rationale and methods for identifying taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, but also genes involved in sweet, bitter, umami, and sour taste perception, and genes involved in other taste cell or taste receptor related activities such as digestive function and digestive related diseases, taste cell turnover, immunoregulation of the oral and digestive tract, and metabolic regulation such as in diabetes and obesity, the genes identified using these methods, and assays for identifying taste modulators (enhancers or blockers) and potential therapeutics using these genes. These compounds have potential application in modulating (enhancing or blocking) taste perception, especially salty taste perception and as potential therapeutics. In addition, this invention relates to novel methods for identifying taste-specific genes that can be used as markers for different taste cell types, including sweet, bitter, umami, sour, salt, and other taste cells in mammals as well as assays that measure the activity of the sweet, bitter, umami, or sour receptor in the presence of these genes to identify modulators of sweet, bitter, umami, and sour taste and to identify therapeutics especially for treating digestive or metabolic disorders, taste loss, and oral infections. Further, the invention provides specific methods of purifying, enriching, isolating or marking desired taste cell subtypes or lineages such as sweet, umami, bitter, salty, sour, fat or stem cells et al. e.g., by use of FACS, magnetic beads or other selection methods that purify, enrich, mark, or eliminate such as by use of labeled cytotoxins, cells that express or do not express one or more taste specific genes.
摘要:
Nucleic acid sequences encoding novel splice variants that encode subunits of an ENaC expressed in human taste tissue are provided. These splice variants when expressed in association with other ENaC subunits, i.e., α, β and γ subunits or α, β and Δ subunits may be used to produce amiloride-insensitive ENACs. The resultant amiloride-insensitive ENaCs are useful in in vitro assays for identifying ENaC modulators that modulate taste (enhance or inhibit), particularly human salty taste.
摘要:
Modified human TRPM8 nucleic acid sequences which are efficiently expressed in human cells and cell-based assays and test kits containing same are provided. These assays identify TRPM8 modulators using cells that express a modified human TRPM8 nucleic acid sequence according to the invention, wherein said sequence has been modified relative to a wild-type human TRPM8 nucleic acid sequence in order to optimize ion channel expression in desired cells. Assays using these modified TRPM8 sequences have been shown to identify compounds that modulate the human TRPM8 ion channel better or comparably to known coolants such as menthol and icilin.
摘要:
This invention relates to novel rationale and methods for identifying human and primate taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, but also genes involved in sweet, bitter, umami, and sour taste perception, and genes involved in other taste cell or taste receptor related activities such as digestive function and digestive related diseases, taste cell turnover, immunoregulation of the oral and digestive tract, and metabolic regulation such as in diabetes and obesity, the genes identified using these methods, and assays for identifying taste modulators (enhancers or blockers) and potential therapeutics using these genes. These compounds have potential application in modulating (enhancing or blocking) taste perception, especially salty taste perception and as potential therapeutics. In addition, this invention relates to novel methods for identifying taste-specific genes that can be used as markers for different taste cell types, including sweet, bitter, umami, sour, salty, and other taste cells in mammals as well as assays that measure the activity of the sweet, bitter, umami, or sour receptor in the presence of these genes to identify modulators of sweet, bitter, umami, and sour taste and to identify therapeutics especially for treating digestive or metabolic disorders, taste loss, and oral infections. Particularly, the genes identified herein and antibodies or oligos thereto can be used as markers to identify and/or purify specific taste cells e.g., from taste cell suspensions by use of FACS or magnetic bead cell selection or other known cell purification and isolation procedures.
摘要:
This invention relates to novel rationale and methods for identifying human and primate taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, but also genes involved in sweet, bitter, umami, and sour taste perception, and genes involved in other taste cell or taste receptor related activities such as digestive function and digestive related diseases, taste cell turnover, immunoregulation of the oral and digestive tract, and metabolic regulation such as in diabetes and obesity, the genes identified using these methods, and assays for identifying taste modulators (enhancers or blockers) and potential therapeutics using these genes. These compounds have potential application in modulating (enhancing or blocking) taste perception, especially salty taste perception and as potential therapeutics. In addition, this invention relates to novel methods for identifying taste-specific genes that can be used as markers for different taste cell types, including sweet, bitter, umami, sour, salty, and other taste cells in mammals as well as assays that measure the activity of the sweet, bitter, umami, or sour receptor in the presence of these genes to identify modulators of sweet, bitter, umami, and sour taste and to identify therapeutics especially for treating digestive or metabolic disorders, taste loss, and oral infections. Particularly, the genes identified herein and antibodies or oligos thereto can be used as markers to identify and/or purify specific taste cells e.g., from taste cell suspensions by use of FACS or magnetic bead cell selection or other known cell purification and isolation procedures.
摘要:
The present invention relates to the elucidation that TRPML3 is involved in salty taste perception in primates including humans and likely other mammals and based thereon high-throughput mammalian and medium-throughput oocyte-based electrophysiological assays for identifying human TRPML3 modulators, preferably TRPML3 enhancers. Compounds that modulate TRPML3 function in the assay are expected to affect salty taste in humans. The inventive electrophysiological assays, such as the two-electrode voltage-clamp technique, facilitate the identification of compounds which specifically modulate human TRPML3. The assays of the invention provide a robust screen useful to detect compounds that facilitate (enhance) or inhibit TRPML3 function. Compounds that enhance or block TRPML3 channel activity should thereby modulate salty taste. In addition, these compounds may be used to regulate sodium excretion, urinary output and other biological functions relating to sodium levels and TRPML3 related functions.
摘要:
This invention relates to novel rationale and methods for identifying human and primate taste-specific genes, including genes involved in salty taste perception, especially human salty taste perception, but also genes involved in sweet, bitter, umami, and sour taste perception, and genes involved in other taste cell or taste receptor related activities such as digestive function and digestive related diseases, taste cell turnover, immunoregulation of the oral and digestive tract, and metabolic regulation such as in diabetes and obesity, the genes identified using these methods, and assays for identifying taste modulators (enhancers or blockers) and potential therapeutics using these genes. These compounds have potential application in modulating (enhancing or blocking) taste perception, especially salty taste perception and as potential therapeutics. In addition, this invention relates to novel methods for identifying taste-specific genes that can be used as markers for different taste cell types, including sweet, bitter, umami, sour, salty, and other taste cells in mammals as well as assays that measure the activity of the sweet, bitter, umami, or sour receptor in the presence of these genes to identify modulators of sweet, bitter, umami, and sour taste and to identify therapeutics especially for treating digestive or metabolic disorders, taste loss, and oral infections. Particularly, the genes identified herein and antibodies or oligos thereto can be used as markers to identify and/or purify specific taste cells e.g., from taste cell suspensions by use of FACS or magnetic bead cell selection or other known cell purification and isolation procedures.
摘要:
This invention relates to the elucidation that TRPML3 is involved in salty taste perception in primates including humans and likely other mammals (given the significance of sodium and other ions to physiological functions and conditions this phenotype is likely strongly conserved in different animals). The invention also relates to the discovery that the TRPML3 gene also modulates one or more of sodium metabolism, sodium excretion, blood pressure, fluid retention, cardiac function and urinary functions such as urine production and excretion. The invention also relates to transgenic animals that have been engineered to express or knock out TRPML3 expression and assays using TRPML3 expressing animals, cells and isolated ion channel polypeptides for identifying compounds that modulate TRPML3-associated functions including salty taste, sodium metabolism, sodium excretion, blood pressure, fluid retention, cardiac function and urinary functions such as urine production and excretion.