Inhibition of signal termination-related kinases by membrane-permeant bitter and sweet tastants: potential role in taste signal termination.
Sweet and bitter taste sensations are believed to be initiated by the tastant-stimulated T1R and T2R G protein-coupled receptor (GPCR) subfamilies, respectively, which occur in taste cells. Although such tastants, with their significantly diverse chemical structures (e.g., sugar and nonsugar sweeteners), may share the same or similar T1Rs, some nonsugar sweeteners and many bitter tastants are amphipathic and produce a significant delay in taste termination (lingering aftertaste). We report that such tastants may permeate rat taste bud cells rapidly in vivo and inhibit known signal termination-related kinases in vitro, such as GPCR kinase (GRK)2, GRK5, and PKA. GRK5 and perhaps GRK2 and GRK6 are present in taste cells. A new hypothesis is proposed in which membrane-permeant tastants not only interact with taste GPCRs but also interact intracellularly with the receptors' downstream shutoff components to inhibit signal termination.
Zubare-Samuelov
Meirav
M
Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel.
Shaul
Merav E
ME
Peri
Irena
I
Aliluiko
Alexander
A
Tirosh
Oren
O
Naim
Michael
M
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D003952:Diagnostic Imaging; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013549:Sweetening Agents / Q000378:metabolism; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000378:metabolism* / Q000648:ultrastructure; D014059:Tongue / Q000378:metabolism / Q000648:ultrastructure; D051552:beta-Adrenergic Receptor Kinases; D000098706:Taste Receptors, Type 2
D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; D000098706:Taste Receptors, Type 2; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases