Inhibition of cAMP-dependent protein kinase A: a novel cyclo-oxygenase-independent effect of non-steroidal anti-inflammatory drugs in adipocytes.
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.
Zentella de Piña
M
M
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., México.
Vázquez-Meza
H
H
Agundis
C
C
Pereyra
M A
MA
Pardo
J P
JP
Villalobos-Molina
R
R
Piña
E
E
D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009288:Naproxen / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D002787:Sterol Esterase / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D010894:Piroxicam; D009288:Naproxen; D011451:Prostaglandin-Endoperoxide Synthases; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase; D001241:Aspirin; C012655:nimesulide