title: Inhibition of platelet aggregation by carbon monoxide-releasing molecules (CO-RMs): comparison with NO donors.
abstract: Carbon monoxide (CO) and CO-releasing molecules (CO-RMs) inhibit platelet aggregation in vitro. Herein, we compare the anti-platelet action of CORM-3, which releases CO rapidly (t                         (½) 1 min), and CORM-A1, which slowly releases CO (t(½) = 21 min). The anti-platelet effects of NO donors with various kinetics of NO release were studied for comparison. The effects of CO-RMs and NO donors were analyzed in washed human platelets (WP), platelets rich plasma (PRP), or whole blood (WB) using aggregometry technique. CORM-3 and CORM-A1 inhibited platelet aggregation in human PRP, WP, or WB, in a concentration-dependent manner. In all three preparations, CORM-A1 was more potent than CORM-3. Inhibition of platelets aggregation by CORM-A1 was not significantly affected by a guanylate cyclase inhibitor (ODQ) and a phosphodiesterase-5 inhibitor, sildenafil. In contrast, inhibition of platelet aggregation by NO donors was more potent with a fast NO releaser (DEA-NO, t                         (½) = 2 min) than slow NO releasers such as PAPA-NO (t                         (½) = 15 min) or other slow NO donors. Predictably, the anti-platelet effect of DEA-NO and other NO donors was reversed by ODQ while potentiated by sildenafil. In contrast to NO donors which inhibit platelets proportionally to the kinetics of NO released via activation of soluble guanylate cyclase (sGC), the slow CO-releaser CORM-A1 is a superior anti-platelet agent as compared to CORM-3 which releases CO instantly. The anti-platelet action of CO-RMs does not involve sGC activation. Importantly, CORM-A1 or its derivatives representing the class of slow CO releasers display promising pharmacological profile as anti-platelet agents.
authors.affiliation: Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland. s.chlopicki@jmrc.org.pl
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lomnicka
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fedorowicz
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Grochal
authors.forename: Karol
authors.initials: K
authors.lastname: Kramkowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mogielnicki
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Buczko
authors.forename: Roberto
authors.initials: R
authors.lastname: Motterlini
mesh_terms: D001880:Boranes / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D002254:Carbonates / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
chemical_list: D001880:Boranes; D002254:Carbonates; D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; D010975:Platelet Aggregation Inhibitors; C503854:sodium boranocarbonate; C476530:tricarbonylchloro(glycinato)ruthenium(II); D002245:Carbon Dioxide