Inhibition of cAMP‐dependent protein kinase A: a novel cyclo‐oxygenase‐independent effect of non‐steroidal anti‐inflammatory drugs in adipocytes

Publisher Website
Google Scholar
Abstract
Summary: 1 Non‐steroidal anti‐inflammatory drugs (NSAIDs) [acetylsalicylic acid (ASS), naproxen, nimesulide and piroxicam] decreased adrenaline‐ or dibutyryl cAMP‐stimulated glycerol release in isolated adipocytes. We aimed to determine the mechanism of this NSAIDs action. 2 Non‐steroidal anti‐inflammatory drugs decreased cAMP‐dependent protein kinase A (PKA) activity in rat adipocyte lysates and in a commercial bovine heart PKA holoenzyme. If added before cAMP, NSAIDs impaired PKA activation by the cyclic nucleotide; however, if PKA was first activated by cAMP, NSAIDs were ineffective. NSAIDs were also ineffective against PKA catalytic subunits. 3 Consequently, NSAIDs lowered hormone‐sensitive lipase translocation from cytosol to lipid storage droplets in adipocytes lysates, the critical event to promote lipolysis. 4 These results indicate that inhibition of PKA activation explains NSAIDs‐induced decrease in adrenaline‐stimulated lipolysis. We suggest that reproduction of such inhibition in nociceptive cells might enhance the understanding of the mechanism underlying the analgesic effects of NSAIDs.