Inhibition of protein kinase A fails to alter mast cell adenosine responsiveness.
Adenosine activates adenylate cyclase and phospholipase C in mast cells and potentiates stimulated mediator release. To determine whether activation of adenylate cyclase is necessary for the effects of adenosine on the mast cell secretory process, a specific inhibitor of cAMP-dependent protein kinase, KT5720, was used. Antigen and adenosine each induced a rapid increase in mast cell cAMP-dependent protein kinase activity within 30 s. Preincubation with KT5720 (100 nM-10 microM) suppressed cAMP-dependent protein kinase activity and inhibited antigen-stimulated beta-hexosaminidase and leukotriene C4 releases. Adenosine retained its ability to potentiate beta-hexosaminidase release in antigen- and A23187-stimulated cells even in the presence of complete cAMP-dependent protein kinase inhibition. Mast cells rendered unresponsive to adenosine-related signals by preincubation with adenosine analogs maintained this hyporesponsiveness after incubation with KT5720. It appears that the abilities of adenosine to augment mast cell degranulation and induce receptor hyporesponsiveness are independent of changes in cAMP.
Marquardt
D L
DL
Department of Medicine, University of California UCSD Medical Center 92103, USA.
Walker
L L
LL
D000241:Adenosine / Q000502:physiology*; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells; D002227:Carbazoles; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011758:Pyrroles / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism*
D002227:Carbazoles; D007211:Indoles; D011758:Pyrroles; D018047:Receptors, Purinergic P1; C057416:KT 5720; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D000241:Adenosine