Phenoxy herbicides and fibrates potently inhibit the human chemosensory receptor subunit T1R3.
We show that phenoxyauxin herbicides and lipid-lowering fibrates inhibit human but not rodent T1R3. T1R3 as a coreceptor in taste cells responds to sweet compounds and amino acids; in endocrine cells of gut and pancreas T1R3 contributes to glucose sensing. Thus, certain effects of fibrates in treating hyperlipidemia and type II diabetes may be via actions on T1R3. Likewise, phenoxy herbicides may have adverse metabolic effects in humans that would have gone undetected in studies on rodents.
Maillet
Emeline L
EL
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
Margolskee
Robert F
RF
Mosinger
Bedrich
B
D015084:2,4-Dichlorophenoxyacetic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology*; D001629:Bezafibrate / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002520:Cercopithecidae; D002995:Clofibric Acid / Q000737:chemistry / Q000494:pharmacology*; D015248:Gemfibrozil / Q000737:chemistry / Q000494:pharmacology; D006540:Herbicides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007210:Indoleacetic Acids / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D013329:Structure-Activity Relationship
D001555:Benzene Derivatives; D006540:Herbicides; D000960:Hypolipidemic Agents; D007210:Indoleacetic Acids; D021122:Protein Subunits; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; C431926:taste receptors, type 1; D015084:2,4-Dichlorophenoxyacetic Acid; D002995:Clofibric Acid; C010571:dichlorprop; D015248:Gemfibrozil; D001629:Bezafibrate; C495512:lactisole