Inhibiting the proton currents in basophils, a rare type
of white blood cell, can stop the release of histamine
and could provide a new target for allergy and asthma drugs
according to a new study by researchers at Rush University
Medical Center in Chicago and the Johns Hopkins Asthma
and Allergy Center in Baltimore. The research is published
in the August 5th issue the Proceedings of the National
Academy of Sciences.
When allergens enter the body, they can be recognized
by IgE antibodies bound to basophils, causing these white
blood cells to release the inflammatory chemical histamine.
Histamine causes several allergic symptoms, including airway
constriction in the lungs, severe itching, hives and swelling,
and is a major cause of asthma.
Basophils are among several cell types that express unique
ion channels called voltage-gated proton channels. Ion
channels open and close providing gates for ions, or charged
electrical particles, to enter or leave cells. This in
turn controls the function of the cell. Voltage-gated proton
channels only allow protons to leave cells and seem to
be designed to rapidly and efficiently force acid from
cells.
Previously the function of the proton channels in basophils
was unknown. Researchers at Rush have determined these
channels are important in the process of histamine release.
"Our research shows that proton channels in basophils
respond vigorously to agents that elicit histamine release," said
Thomas DeCoursey, PhD, professor of molecular biophysics
and physiology at Rush. "We also determined that histamine
was inhibited by zinc at concentrations that inhibit proton
currents, consistent with the idea that proton channel
activity is linked to basophil activation."
According to DeCoursey, this research points to a new
target for drug developers. Prevent the channel from working
and that would stop the release of histamine. Currently,
the most potent inhibitor is zinc, but zinc is toxic in
high concentrations and the body regulates zinc levels
very closely. The goal is to develop a more selective inhibitor
of the proton channel that would bind to it and prevent
its activity without doing harm.
"It is exciting to discover a novel function for
proton channels," said DeCoursey. "We believe
this research could lead to new approaches to reduce the
potentially deadly consequences of asthma and allergic
reactions."
Rush University Medical Center
1700 W Van Buren, Ste. 250
Chicago, IL 60012
United States
http://www.rush.edu
