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Common Herbicides Block Important Nutrient Sensor in Humans

(Beyond Pesticides, October 15, 2009) New research from the Monell Center and the Mount Sinai School of Medicine reveals that phenoxy herbicides block T1R3, a nutrient-sensing taste receptor found in the pancreas and intestines of humans. These commonly used herbicides were not previously known to act on the T1R3 receptor, nor has any animal testing revealed any indication of this. The specific effects are unique to humans; thus, phenoxy herbicides may have adverse metabolic effects in humans that would have gone undetected in studies on rodents.

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.

The study, co-authored by Emeline Maillet from the Department of Neuroscience at Mount Sinai School of Medicine and co-author Robert Margolskee of Monell, and published online in the Journal of Medicinal Chemistry, tests the ability of two classes of chemical compounds to block the T1R3 receptor. Lipid lowering fibrate drugs used to treat high blood cholesterol; and phenoxy herbicides used in agriculture and in lawn care to control broad-leaf weeds. These two chemical compounds were selected based on their strong structural similarity to lactisole, a sweet taste inhibitor that exerts its taste effects by blocking T1R3.

Study researchers used an in vitro preparation to find that both classes of compounds, -phenoxy herbicides, along with fibrates, potently blocked activation of the human sweet taste receptor, acting at micromolar concentrations to inhibit binding of sugars to the T1R3 component of the receptor.

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.

Popular phenoxy herbicides include MCPA, Mecoprop (MCPB), and 2,4-D, one of the most extensively used herbicides in the world. According to the U.S. Environmental Protection Agency’s (EPA) Pesticide Industry and Usage Report, 2,4-D is the most commonly used pesticide in the nonagricultural sector and the fifth most commonly used pesticide in the nonagricultural sector in the U.S. It is a selective herbicide, used to kill broadleaf weeds with little to harm to grass crops. It is a plant growth regulator and mimics the natural plant growth hormone.

Phenoxy herbicides have been linked to a host of adverse human impacts, as well as water contamination and toxicity to aquatic organisms. Previous studies have shown that exposure to MCPA can more than double one’s risk of developing non-Hodgkin lymphoma (NHL). Another study published last month found that occupational 2,4-D exposure almost triples the risk of Parkinson’s disease compared to those reporting no exposure to the agent.

It is important to note that the implications of this study, as suggested by Dr. Mosinger, highlight the significance of testing chemicals intended for human use on human tissues, because these tests did not have the same results on lab rats. “The metabolic consequences of short- and long-term exposures of humans to phenoxy-herbicides are unknown. This is because most safety tests were done using animals, which have T1R3 receptors that are insensitive to these compounds,” he said.

Dr. 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.

These highly toxic chemicals can be replaced by cost-competitive and effective management practices widely used in organic agriculture and lawn care. For information on ways to manage weeds without the use of phenoxy-herbicides, please refer to Beyond Pesticides’ Lawns and Landscapes page.

Source: Science Daily


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