[Cytoprotective action of guanylate cyclase stimulators on human leukocytes].
An original experimental model has been presented for studying of cytoprotection of non-stimulated leukocytes. The model consists in determining of a degree of inhibition of the release of lactic acid dehydrogenase (LDH) by isolated human neutrophils (PMNs) in the course of their "ageing" at the room temperature (22 degrees C). Using this model for the first time, cytoprotective action was pointed-out of following compounds: NO (EDRF) in aqueous solution; natrium nitroprusside; active metabolite of molsidomine--SIN-1; N-acetyl-S-nitroso-penicillamine (SNAP) which are believed to owe their anti-platelet and vasodilatory activity to stimulation of cyclic-GMP--and iloprost (a stable prostacyclin analogue) and prostaglandin E2 (PGE2) which activate cyclic AMP. Effectiveness of cytoprotective action of these compounds increased as follows: NO (IC50 = 58.4) less than PGE2 (IC50 = 38) less than SIN-1 (IC50 = 9.2) less than SNAP (IC50 = 3.2) less than natrium nitroprusside (IC50 = 1.2) less than iloprost (IC50 = 0.2)(nmoles/5 x 10(6) PMNs; moreover, iloprost and SIN-1 showed a synergic action. Among ++nitroso-vasodilators, nitroglycerin had no cytoprotective action; it may indicate that to achieve cytoprotection in leukocytes a nitro- vasodilator should contain in its chemical structure -NO group and not -NO3 group, as it is in nitroglycerin. In neutrophils stimulated with calcium ionophore, arachidonic acid or FMLP, nitro-vasodilators are of no influence on production of superoxide anions O2-, hydroxyeicosatetraenoic acids (5-HETE and 12-HETE) and leukotriene B4. A hypothesis has been put forward on the relationship of function of c-GMP and c-AMP in the mechanism of cytoprotection of human leukocytes.
Trabka-Janik
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Katedry Farmakologii, Akademii Medycznej im. M. Kopernika w Krakowie.
D001792:Blood Platelets / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000502:physiology*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology
D007770:L-Lactate Dehydrogenase; D006162:Guanylate Cyclase; D016285:Iloprost; D015232:Dinoprostone
Cytoprotekcyjne działanie stymulatorów cyklazy guanylowej na ludzkie leukocyty.