Korean J Physiol Pharmacol.
1997 Feb;1(1):97-105.
Comparison of regulatory action of cAMP and cGMP on the activation of
neutrophil responses
- Affiliations
-
- 1Department of Pharmacology, College of Medicine, Chung-Ang University,
Seoul 156-756 South Korea.
Abstract
-
The regulatory role of cyclic nucleotides in the expression of
neutrophil responses has been examined. fMLP-stimulated superoxide
production in neutrophils was inhibited by dibutyryl adenosine
3',5'-cyclic monophosphate (DBcAMP), histamine, adenosine +
theophylline, cAMP elevating agents, and 8-bromoguanosine 3',5'-cyclic
monophosphate (8-BrcGMP) and sodium nitroprusside, cGMP elevating
agents. Staurosporine, a protein kinase C inhibitor, genistein, a
protein tyrosine kinase inhibitor and chlorpromazine, a calmodulin
inhibitor, inhibited superoxide production by fMLP, but they did not
further affect the action of DBcAMP on the stimulatory action of fMLP.
DBcAMP, histamine, adenosine + theophylline and genistein inhibited
myeloperoxidease release evoked by fMLP, whereas BrcGMP, sodium
nitroprusside and staurosporine did not affect it. The elevation of
(Ca2+)-i evoked by fMLP was inhibited by genistein and chlorpromazine
but was not affected by staurosporine. DBcAMP exerted little effect on
the initial peak in (Ca2+)-i response to fMLP but effectively
inhibited the sustained rise. On the other hand, BrcGMP significantly
inhibited both phases. fMLP-induced Mn-2+ influx was inhibited by
either DBcAMP or BrcGMP. These results suggest that fMLP-stimulated
neutrophil responses may be regulated by cAMP more than cGMP. cAMP and
cGMP appear not affect stimulated responses by direct protein kinase C
activation. Their regulatory action on the stimulated neutrophil
responses may be not influenced by other activation processes.