Inhibition of collagen- and ADP-induced platelet aggregation by substance P in vivo: involvement of endothelium-derived relaxing factor.
We examined the effect of substance P, a potent stimulator of endothelium-derived relaxing factor (EDRF) release, on responses to collagen and adenosine 3',5'-diphosphate (ADP) in an in vivo model of platelet aggregation. Substance P inhibited platelet aggregation induced in vivo by both collagen and ADP. This anti-platelet effect was particularly pronounced against collagen-induced aggregation and was prevented by prior administration of haemoglobin (Hb), a known inhibitor of EDRF-mediated responses. Collagen-induced platelet aggregation in vitro was unaffected by a concentration of substance P equivalent to that achieved in plasma following in vivo administration. This study provides a clear demonstration of the anti-platelet activity of EDRF in vivo and an indication that its effectiveness may depend on the aggregating agent used.
Department of Pharmacology, Fisons plc-Pharmaceutical Division, Leicestershire, England.
R G
RG
Humphries
W
W
Tomlinson
S E
SE
O'Connor
P
P
Leff
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors*; D000818:Animals; D003094:Collagen / Q000037:antagonists & inhibitors*; D015232:Dinoprostone / Q000494:pharmacology; D006168:Guinea Pigs; D006454:Hemoglobins / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology*
D006454:Hemoglobins; D009569:Nitric Oxide; D013373:Substance P; D000244:Adenosine Diphosphate; D003094:Collagen; D015232:Dinoprostone