Vioxx Research - Osteoarthritis, Side-effects, Trials, Stroke, Heart Attack

Vioxx Research Today is a free monthly online journal that collates and summarizes the latest research about Vioxx, including details on osteoarthritis, side-effects, trials, stroke, heart attack.


Vioxx Research Today

Home

View Latest Issue

Information About Vioxx

Books on Vioxx

Advertising in Research Today

View Other Research Today Publications



Mechanisms of K(v)2.1 channel inhibition by celecoxib - modification of gating and channel block.

Frolov R, Bondarenko V, Singh S

Department of Pharmacology and Toxicology, State University of New York, Buffalo, New York, USA.

Background and purpose: Selective cyclooxygenase-2 (COX-2) inhibitors such as rofecoxib (Vioxx) and celecoxib (Celebrex) were developed as NSAIDs with reduced gastric side effects. Celecoxib has now been shown to affect cellular physiology via an unexpected, COX-independent, pathway - by inhibiting K(v)2.1 and other ion channels. In this study, we investigated the mechanism of the action of celecoxib on K(v)2.1 channels. Experimental approach: The mode of action of celecoxib on rat K(v)2.1 channels was studied by whole-cell patch-clamping to record currents from channels expressed in HEK-293 cells. Key results: Celecoxib reduced current through K(v)2.1 channels when applied from the extracellular side. At low concentrations (</=3 microM), celecoxib accelerated kinetics of activation, deactivation and inactivation. Recovery of rat K(v)2.1 channels from inactivation could be characterized by two components, with celecoxib selectively accelerating the slow component of recovery at </=10 microM. At >3 microM, celecoxib led to closed-channel block with relative slowing of activation. At 30 microM, it additionally induced open-channel block that manifested in use-dependent inhibition and slower recovery from inactivation. Conclusions and implications: Celecoxib reduced current through K(v)2.1 channels by modifying gating and inducing closed- and open-channel block, with the three effects manifesting at different concentrations. These data will help to elucidate the mechanisms of action of this widely prescribed drug on ion channels and those underlying its neurological, cardiovascular and other effects.

Published 17 December 2009 in Br J Pharmacol.
Full-text of this article is available online (may require subscription).

Place a permanent text-link or advertisement here.

© 2004-2014 Vioxx Research Today. All Rights Reserved.



Vioxx Research Today Archive:

Volume 1 (2004)
  Issue 1 (November)
  Issue 2 (December)

Volume 2 (2005)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 3 (2006)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 4 (2007)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 5 (2008)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 6 (2009)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 7 (2010)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 8 (2011)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 9 (2012)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 10 (2013)
  Issue 1 (January)
  Issue 2 (February)
  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
  Issue 9 (September)
  Issue 10 (October)
  Issue 11 (November)
  Issue 12 (December)

Volume 11 (2014)
  Issue 1 (January)
  Issue 2 (February)



Vioxx Books

Osteoarthritis Laminated Reference Guide (Quickstudy: Health)

Osteoarthritis Laminated Reference Guide (Quickstudy: Health)