title: Inhibition by hydrogen sulfide of rabbit platelet aggregation and calcium mobilization.
abstract: Hydrogen sulfide (H2S), a gasotransmitter, plays a variety of roles in the mammalian body including the cardiovascular system. Given evidence that H2S donors including NaHS inhibit human platelet aggregation, we examined and characterized the effects of NaHS on rabbit platelet aggregation and cytosolic Ca(2+) mobilization. Rabbit platelet aggregation was determined in platelet-rich plasma (PRP) and washed platelets. Intracellular Ca(2+) levels were monitored in Fura2-loaded washed platelets. NaHS prevented rabbit platelet aggregation induced by collagen or ADP, and the effective concentration range of NaHS was 0.1-0.3 mM in PRP and 1-3 mM in washed platelets. In washed platelets, NaHS attenuated cytosolic Ca(2+) mobilization induced by collagen or ADP and also reduced platelet aggregation induced by ionomycin, a Ca(2+) ionophore. The anti-platelet effect of NaHS was blocked by an adenylyl cyclase inhibitor and enhanced by a phosphodiesterase inhibitor. H2S thus suppresses rabbit platelet aggregation by interfering with both upstream and downstream signals of cytosolic Ca(2+) mobilization in a cAMP-dependent manner.
authors.affiliation: Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3–4–1 Kowakae, Higashi-Osaka 577–8502, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Satoko
authors.initials: S
authors.lastname: Kubo
authors.forename: Maho
authors.initials: M
authors.lastname: Tsubota-Matsunami
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D002118:Calcium; D006862:Hydrogen Sulfide