Nitridergic platelet pathway activation by hementerin, a metalloprotease from the leech Haementeria depressa.
Hementerin (HT) is an 80 kDa fibrino(geno)lytic metalloprotease, purified from saliva of the leech Haementeria depressa. In the present report, the effect of HT on several functional parameters of human platelets was assessed. HT inhibited platelet aggregation and ATP release induced by different agonists such as ADP, adrenaline, collagen, thrombin, and arachidonic acid. HT did neither modify the expression of platelet glycoproteins (Ib, IIb-IIIa, Ia-IIa, IV) nor intraplatelet fibrinogen levels, whereas it markedly decreased CD62P and CD63 levels after the stimulation with thrombin. HT significantly increased thrombin-induced platelet Ca2+ intracellular levels, cGMP content and nitric oxide synthase (NOS) activity. The effect of HT on platelet aggregation was reversed by two NOS inhibitors, N(omega)-Nitro-L-arginine methyl ester and 2 N(G)-Nitro-L-arginine. In summary, these results indicate that HT is an effective inhibitor of human platelet aggregation, presumably through activation of the platelet's nitridergic pathway.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005340:Fibrinogen / Q000032:analysis; D007865:Leeches / Q000201:enzymology*; D045726:Metalloproteases / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D014020:Tissue Extracts / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D014020:Tissue Extracts; D009569:Nitric Oxide; C011476:hementerin; D000255:Adenosine Triphosphate; D005340:Fibrinogen; D019001:Nitric Oxide Synthase; D045726:Metalloproteases; D013917:Thrombin; D006152:Cyclic GMP; D002118:Calcium