This is one in a series of articles written by research students in the University of Toledo College of Medicine (the former Medical College of Ohio) Biomedical graduate program exploring basic issues of human health.
Have you ever tried the “Saltine challenge?”
This challenge requires you to eat six Saltines in 60 seconds. If completed successfully, your mouth is so dry that swallowing becomes painful and nearly impossible.
For those afflicted with Sjogren’s Syndrome, an autoimmune disorder characterized by dry mouth and dry eyes, this unpleasant sensation is a way of life. Sjogren’s affects roughly 4 million Americans, mostly women.
Sjogren’s earned a national spotlight in 2011 when professional tennis player Venus Williams withdrew from the U.S. Open after announcing that she had been diagnosed with this disorder. While dry mouth is not life threatening, sufferers are more at risk for dental diseases, vocal cord bleeding, joint pain and general fatigue that severely affects their quality of life.
Our research laboratory at the University of Toledo College of Medicine and Life Sciences, focuses primarily on effects of the disease that cause dry mouth.
Sjogren’s Syndrome targets organs located in the head and neck region known as salivary glands. These glands make a watery, protein-rich liquid called saliva needed for chewing, swallowing, and digestion.
Salivary glands produce saliva in response to signals from neurons (nerve cells). How does this occur?
We know that very specific neuronal signals trigger calcium release from pools within your salivary gland cells. Calcium is a mineral that is essential for life because it has numerous functions inside the cells in your body. Once neurons trigger calcium release, this mineral then releases saliva from salivary glands.
A good analogy would be a person (neuron) using a button on a remote control (calcium) to turn to a specific channel on the television (saliva). Early stage Sjogren’s Syndrome features a lack of response to specific triggers by neurons, meaning that calcium is no longer released to signal the release of saliva (the person cannot find the correct channel with the remote). The result is chronic dry mouth.
My research is to identify targets within salivary gland cells that can be selectively used for calcium release to lessen the severity of dry mouth.
We are investigating locations within salivary gland cells that are rich in calcium that can be called “special stores.” Our research first established that salivary gland cells contain an abundant number of these special stores. We then discovered these special stores also participate in large-scale calcium release only if a molecule called “cyclic adenosine monophosphate” is increased within salivary gland cells. Cyclic adenosine monophosphate, like calcium, is generated following specific neuronal signals (using a different button on the remote).
The discovery that special stores contribute to large- scale calcium release was made using a drug that poisoned these special stores. This drug stopped the release of calcium even in the presence of cyclic adenosine monophosphate. We believe cyclic adenosine monophosphate activates a cellular factory that manufactures a “key” that then unlocks special stores, allowing calcium release.
This key is another molecule called nicotinic acid adenine dinucleotide phosphate. To experimentally support our belief, we blocked this molecular key’s actions, which prevented the unlocking of special stores and calcium release, even when the factory was still producing the key molecule that normally triggers saliva.
The experiments performed within our research laboratory have shown that the nicotinic acid adenine dinucleotide phosphate key is a potential drug target that would provide much needed therapy for increasing saliva secretion to combat dry mouth. In future studies we plan to test our results in a mouse model of Sjogren’s Syndrome, as well as in salivary tissue from Sjogren’s patients.
Jack Imbery is a PhD student in the Neurosciences and Neurological Diseases track at The University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Jack is doing his PhD research in the laboratory of Dr. David Giovannucci in the Department of Neurosciences. For more information, contact John.Imbery@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical
First Published April 6, 2015, 4:00 a.m.