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KMID : 0811719970010010097
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Korean Journal of Physiology & Pharmacology
1997 Volume.1 No. 1 p.97 ~ p.105
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Comparision of Regulatory Action of cAMP and cGMP on the Activation of Neutrophil Responses
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Chang-Hwang Han
Young-Chul Yoon/Yong-Kyoo Shin/Eun-Sook Han/Chung-Soo Lee
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Abstract
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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 Mn2+ 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.
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KEYWORD
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Cyclic nucleotides, Protein kinase and calmodulin inhibitors, Neutrophils,
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