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.