Overview
- Brueggemann, L.I. et al. (2012) Am. J. Physiol. Lung Cell. Mol. Physiol. 302, L120.
Alomone Labs 2,5-dimethylcelecoxib enhances KCNQ2/KCNQ3 heteromeric channels expressed in Xenopus oocytes.A. Time course of KCNQ2/KCNQ3 current enhancement by 10 and 100 µM 2,5-dimethylcelecoxib (#D-150) as measured at -40 mV. Currents were elicited by application of voltage ramp from a holding potential of -100 mV to 0 mV (800 msec). B. Superimposed example traces of current responses before and during perfusion of 10 and 100 µM 2,5-dimethylcelecoxib, as indicated (part of the response to ramp stimulation).
KV7 (KCNQ) channels are voltage-gated potassium channels. These channels are mainly responsible for the cardiac and auditory IKs current and the neuronal M-current but can be found in other tissues as well. Voltage-gated potassium channels are tetramers of α-subunits, which surround a K+-selective pore1. The five different KCNQ subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain tail. This domain is a self-assembling, parallel, four-stranded coiled coil2.
2,5-Dimethylcelecoxib (DMC) is a synthetic opener of KCNQ channels in smooth muscle cells. It is a derivative of Celecoxib without its COX-2 inhibitory function. In asthma and other lung diseases, airways become hyperconstricted because of the secretion of various endogenous substances. DMC causes an increase in KCNQ currents and restores current amplitudes in guinea pig ASMC (air smooth muscle cells). This effect is also seen after the application of bronchoconstrictors such as methacholine and histamine, suggesting that DMC can regulate and dilate airway diameter in bronchoconstricting diseases3. DMC is a potent activator of apoptotic pathways and also suppresses production of prostaglandins in vitro by inhibiting cytokine-triggered upregulation of microsomal PGE-synthase-1. These properties may be valuable in the research of cancer4.
