INVOLVEMENT OF PLATELET CYCLIC-GMP BUT NOT CYCLIC-AMP SUPPRESSION IN LEUKOCYTE-DEPENDENT PLATELET-ADHESION TO ENDOTHELIAL-CELLS INDUCED BY PLATELET-ACTIVATING-FACTOR IN-VITRO
M. Hirafuji et al., INVOLVEMENT OF PLATELET CYCLIC-GMP BUT NOT CYCLIC-AMP SUPPRESSION IN LEUKOCYTE-DEPENDENT PLATELET-ADHESION TO ENDOTHELIAL-CELLS INDUCED BY PLATELET-ACTIVATING-FACTOR IN-VITRO, British Journal of Pharmacology, 117(2), 1996, pp. 299-304
1 Incubation of endothelial cells with platelets in the absence or the
presence of PAF (10 nM) markedly increased platelet cyclic AMP levels
, which were significantly decreased by indomethacin (3 mu M). Coincub
ation of endothelial cells and platelets with polymorphonuclear leukoc
ytes (PMNs) did not change the platelet cyclic AMP levels. 2 Incubatio
n of endothelial cells with platelets in the absence of PAF increased
platelet cyclic GMP levels, which were increased 3.5 fold by PAF. Thes
e cyclic CTMP levels were significantly decreased by N-G-nitro-L-argin
ine (100 mu M), and completely by methylene blue (10 mu M). When endot
helial cells and platelets were co-incubated with PMNs, the cyclic GMP
level in the cell mixture was 42.5 and 65.3% lower than that in endot
helial cells and platelets without and with PAF stimulation, respectiv
ely. 3 PAF induced platelet adhesion to endothelial cells only when PM
Ns were present. Methylene blue dose-dependently potentiated the PMN-d
ependent platelet adhesion induced by PAF, although it had no effect i
n the absence of PMNs. 4 Sodium nitroprusside and 8-bromo cyclic GMP b
ut not dibutyryl cyclic AMP significantly, although partially, inhibit
ed the platelet adhesion. Inhibition of cyclic GMP-specific phosphodie
sterase by zaprinast slightly inhibited the PMN-induced platelet adhes
ion and potentiated the inhibitory effect of 8-bromo cyclic GMP, while
these drugs markedly inhibited the adhesion of platelet aggregates in
duced by PMN sonicates. 5 These results suggest that the impairment by
activated PMNs of EDRF-induced platelet cyclic GMP formation is invol
ved in part in the mechanism of PMN-dependent platelet adhesion to end
othelial cells induced by PAF in vitro. The precise mechanism still re
mains to be clarified.