Why the face? UW researchers find clue to drugs' bad taste

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Why the face? UW researchers find clue to drugs' bad taste

Finding may help develop drugs that don't cause dry mouth
Sarah C.B. Guthrie

Taking a medication as prescribed is critical to a drug's effectiveness. But for some people, taking medications literally turns their stomach – and if a medication leaves a persistently bitter taste, many people, especially children and elderly patients, will take it inconsistently or not at all.

Hundreds of prescription drugs can adversely influence a patient's sense of taste and smell, says the Physician’s Desk Reference. These adverse effects frequently linger long after a patient consumes the drug, and can significantly affect the patients’ quality of life, dietary choices – even their emotional state.

Very little is known about how drugs are secreted into saliva before they can bind to taste receptors in the mouth, information necessary to counter this effect. 

Joanne Wang is a UW professor of pharmaceutics and affiliate investigator at the Fred Hutchinson Cancer Research Center
picture of Dr. Joanne Wang

In the online Journal of Biological Chemistry, Joanne Wang’s research team in the University of Washington School of Pharmacy describe a novel mechanism for active drug accumulation and secretion in salivary gland epithelial cells that leads to the lingering bad taste of metformin, a frontline prescription drug used to treat type 2 diabetes.

“Dr. Wang’s lab has identified a transporter protein in the salivary gland that takes up drug compounds from the circulating blood and transfers them to the saliva they produce, giving us new insight into how certain medications change how foods taste,” said Dr. Richard Okita of the National Institute of General Medical Sciences, which partially funded the research.

“This discovery could potentially be used in drug development to prevent excessive accumulation of a drug in saliva and reduce related conditions such as drug-induced dry mouth.”

The researchers found that metformin was actively transported into salivary glands of mice to levels as high as those seen in the kidney and liver. By contrast, drug accumulation in salivary glands didn’t occur when a specific gene was deleted.

These studies shed new light on the molecular mechanisms behind drug-induced taste disorders and are the first time that the mechanisms have been demonstrated for active drug accumulation and secretion in salivary glands. 
The primary function of salivary glands is to secrete saliva, which plays an important role in oral health, nutrient digestion, and immunity to microbial infection.  A certain amount of saliva is secreted each day in healthy adults, but if the glands don’t work properly, it can lead to "dry mouth," another side effect associated with medication use.  The discovered mechanism can lead to very high levels of drugs accumulating in the salivary glands, which may interfere with the normal function of the glands, leading to drug-induced dry mouth syndrome. 
Taste of a Pill: Organic Cation Transporter 3 Mediates Metformin Accumulation and Secretion in Salivary Glands” may be viewed online and will be published in the October 2014 print issue of the Journal of Biological Chemistry. This work was supported by National Institutes of Health grants GM066233, GM07750 and HD047892.