Researchers at the University of Alberta have discovered a basic cellular process the body uses to balance pH in cells--also critical to recovery following a heart attack--is compromised by certain novel COX-2 inhibitors.
Bicarbonate transporters, enzymes critical to maintaining this delicate balance of bicarbonate across the cell membrane, are potently inhibited from doing their work by some clinically used non-steroidal anti-inflammatory drugs such as celecoxib, the active ingredient in Celebrex.
Celecoxib is an effective anti-inflammatory drug because of its effects on the enzyme cyclooxygenase-2 (COX-2). The work from the Casey laboratory indicates that the reported side-effects of celecoxib may result from their unintended inhibition of the body's ability to move bicarbonate.
The work was headed up by principal researcher Joe Casey, a University of Alberta physiology professor.
Bicarbonate (HCO3-) is the primary pH buffer of our bodies and the primary waste product of cellular energy production. Movement of the base, HCO3-, into or out of a cell will alkalinize or acidify the cell. Our cells carefully control the concentration and movement of HCO3- across the plasma membrane by regulation of bicarbonate transport proteins (BT) that can rapidly catalyse the transmembrane movement of HCO3-. The focus of Dr. Casey's laboratory's research is to understand the processes of transmembrane HCO3- transport at the molecular and cellular levels.
The work will appear in the November 23 issue of Molecular Membrane Biology. Co-researchers included Patricio Morgan, a postdoctoral research fellow in the Casey Research Group, and Claudiu Supuran, of the University of Florence, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica,Sesto Fiorentino, Italy.
Dr. Casey's work is funded by the Canadian Institutes of Health Research and the Heart and Stroke Foundation. Dr. Casey is a Senior Scholar of the Alberta Heritage Foundation for Medical Research.