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Naunyn Schmiedebergs Arch Pharmacol


Title:"Differential inhibition and potentiation of chemoattractant-induced superoxide formation in human neutrophils by the cell-permeant analogue of cyclic GMP, N2,2'-O-dibutyryl guanosine 3':5'-cyclic monophosphate"
Author(s):Ervens J; Schultz G; Seifert R;
Address:"Institut fur Pharmakologie, Freie Universitat Berlin, Federal Republic of Germany"
Journal Title:Naunyn Schmiedebergs Arch Pharmacol
Year:1991
Volume:343
Issue:4
Page Number:370 - 376
DOI: 10.1007/BF00179041
ISSN/ISBN:0028-1298 (Print) 0028-1298 (Linking)
Abstract:"Human neutrophils possess a superoxide (O2-)-forming NADPH oxidase which is activated by the chemoattractants, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), complement C5a, platelet-activating factor and leukotriene B4. We studied the roles of cAMP and cGMP in the regulation of O2- formation using the cell-permeant analogues of cyclic nucleotides, N6,2'-O-dibutyryl adenosine 3':5'-cyclic monophosphate (Bt2cAMP) and N2,2'-O-dibutyryl guanosine 3':5'-cyclic monophosphate (Bt2cGMP). Bt2cAMP inhibited O2- formation induced by these chemoattractants to similar extents. Bt2cGMP as low as 10 mumol/l significantly inhibited O2- formation induced by fMet-Leu-Phe at a submaximally effective concentration (50 nmol/l), and Bt2cGMP was more effective in diminishing O2- formation than Bt2cAMP. In contrast, Bt2cGMP did not affect O2- formation induced by fMet-Leu-Phe at a maximally effective concentration (1 mumol/l). Bt2cGMP (0.1 and 1 mmol/l) enhanced O2- formation induced by 0.1 mumol/1 C5a by 23% and 49%, respectively, and Bt2cGMP antagonized inhibition of O2- formation caused by Bt2cAMP. Bt2cGMP inhibited platelet-activating factor-induced O2- formation to a lesser extent than Bt2cAMP and had no effect on that induced by leukotriene B4. Bt2cAMP and Bt2cGMP had no effect on O2- formation induced by NAF, gamma-hexachlorocyclohexane, phorbol myristate acetate, A 23187 and arachidonic acid. Our data suggest that: 1. Bt2cAMP generally inhibits chemoattractant-stimulated O2- formation. 2. Bt2cGMP inhibits fMet-Leu-Phe- and platelet-activating factor-stimulated O2- formation but potentiates C5a-induced O2- formation.(ABSTRACT TRUNCATED AT 250 WORDS)"
Keywords:Bucladesine/*pharmacology Cyclic AMP/analogs & derivatives Cyclic GMP/analogs & derivatives Dibutyryl Cyclic GMP/*pharmacology Humans Neutrophils/*drug effects/metabolism Sex Attractants/*pharmacology Superoxides/*isolation & purification;
Notes:"MedlineErvens, J Schultz, G Seifert, R eng Comparative Study Research Support, Non-U.S. Gov't Germany 1991/04/01 Naunyn Schmiedebergs Arch Pharmacol. 1991 Apr; 343(4):370-6. doi: 10.1007/BF00179041"

 
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