Certain common herbicides and lipid-lowering fibrate drugs act in humans to block T1R3, a nutrient-sensing taste receptor also present in intestine and pancreas, according to new research from the Monell Center and the Mount Sinai School of Medicine.
Commonly used in agriculture and medicine, these chemical compounds were not previously known to act on the T1R3 receptor.The T1R3 receptor is a critical component of both the sweet taste receptor and the umami (amino acid) taste receptor. First identified on the tongue, emerging evidence indicates that T1R3 and related taste receptors also are located on hormone-producing cells in the intestine and pancreas.
These internal taste receptors detect nutrients in the gut and trigger the release of hormones involved in the regulation of glucose homeostasis and energy metabolism.
"Compounds that either activate or block T1R3 receptors could have significant metabolic effects, potentially influencing diseases such as obesity, type II diabetes and metabolic syndrome," noted Monell geneticist and study leader Bedrich Mosinger, M.D., Ph.D.
In the study, published online in the Journal of Medicinal Chemistry, researchers tested the ability of two classes of chemical compounds to block the T1R3 receptor. The compounds – fibrates and phenoxy-herbicides – were selected based on their strong structural similarity to lactisole, a sweet taste inhibitor that exerts its taste effects by blocking T1R3.
Fibrates are a class of drugs frequently used to treat lipid disorders such as high blood cholesterol and triglycerides. Phenoxy-herbicides are used in agriculture to control broad-leaf weeds; the best known, 2,4-D, is one of the most extensively used herbicides worldwide.
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Additional testing revealed that the inhibitory effect of both fibrates and phenoxy-herbicides on the T1R3 receptor is specific to humans. That is, the ability of these compounds to block the receptor did not generalize across species to the rodent form of the receptor.
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The ability of fibrate drugs to interact with T1R3 receptors also was previously unknown. The study findings suggest that these receptors might be an important pharmacological target of first-generation fibrates, such as clofibrate, which were believed to act on a different receptor to affect lipid metabolism. Newer fibrate drugs are more specific for the second receptor and interact less with the T1R3 receptor.
Mosinger points out that little is known about how T1R3 blockade affects hormone levels and metabolism. "Given the number of compounds used in agriculture, medicine and the food industry that may affect human T1R3 and related receptors, more work is needed to identify the health-related effects of exposure to these compounds," he said.
Source-Eurekalert
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