The fragrant black liquid swirling into his cup is a frequent and welcome sight to Nevin Lambert. Coffee also contains his life's work, and may yield clues into a perplexing problem with painkillers.
Dr. Lambert, a researcher at the Medical College of Georgia, is studying the receptor system in the brain that sparks or shuts down neurons.
Receptors are chemical switches that sit on or near the cell surface. They interact with certain other molecules that can signal the cell to react. One of those receptors involves adenosine, a byproduct of the cellular fuel adenosine triphosphate, which constantly lurks in the spaces between neurons, Dr. Lambert said. Adenosine interacts with an adenosine A1 receptor on neurons, which then can prevent the cell from releasing neurotransmitters, or shut it down.
"It really basically puts you to sleep," Dr. Lambert said. "In fact, that's what some people think adenosine is there for."
Caffeine binds with the adenosine receptor and prevents adenosine from interacting with it.
"It is thought that the stimulatory effects of caffeine have to do with blocking A1 receptors," thus keeping neurons more active, Dr. Lambert said.
The A1 receptors are in a class of receptors that include opiate receptors, which react to painkillers such as morphine. Over a long period of time, patients build up tolerance to the morphine, Dr. Lambert said.
"Patients that are given a lot of morphine, if they are in pain for example from cancer, eventually have to start wearing morphine pumps because the amount of morphine that you have to give to somebody goes sky-high," Dr. Lambert said.
The MCG researchers chose to study the adenosine receptors because they are more numerous on the neurons they studied in the lab. In Dr. Lambert's lab, graduate student Jonathon Wetherington subjected neurons to continuous doses of adenosine and studied the response of the receptors. He noticed a curious thing, based on where the receptors were located on the neurons.
"It seems as though the adenosine receptors on the dendrites - that's the input side of the cell - stop responding within an hour or two, whereas those on the presynaptic terminals - the output stage - continue to respond for a day or two," Dr. Lambert said. "They take an awful lot longer to desensitize. This could explain a number of things" about how tolerance builds.
The next step may be to study opiate receptors directly in living slices of rat brain tissue to see if they have the same response.
For Tara Kattine, the medical director of St. Joseph Hospice and Palliative Care, and others who treat terminally ill patients, morphine tolerance is less of an issue because they have learned to use other drugs to help relieve the symptoms, she said. But for some patients, it would be nice to have a mechanism to defeat the tolerance, she said.
"Especially those in intractable pain," Dr. Kattine said.
Blocking one kind of adenosine receptor may also help in treating Parkinson's disease, in which the brain's "braking mechanism" is overactive and blocking the receptor that "blocks some of those braking mechanisms," said Kapil Sethi, the director of the MCG Movement Disorders Clinic.
"That's the big idea right now," Dr. Sethi said.
MCG will soon be testing a drug that blocks that kind of receptor, Dr. Sethi said.
For Dr. Lambert, the caffeine connection is personal. He manages to down a couple of pots a day and is especially fond of Costa Rican dark roast.
"I buy my beans in 10-pound bags," he said.
Reach Tom Corwin at (706) 823-3213 or firstname.lastname@example.org.
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