Prothrombotic roles of substance-P, neurokinin-1 receptors and leukocytes in the platelet-dependent clot formation in whole blood.
A number of types of non-neuronal cells including leukocytes have been confirmed to possess substance-P and its specific neurokinin-1 receptor (NK1R), while the pathophysiological roles of substance-P in these cells remain to be established. Effects of substance-P through NK1R on platelet-dependent clot formation were evaluated by using an oscillating-probe viscoelastometer. The clot signal, indicative of the clot strength in blood-derived samples, was measured after the stimulation with celite and Ca(2+). Substance-P (10 nM) increased the clot signal of whole blood obtained from healthy volunteers, especially modulating the platelet-dependent distinctive peak in traces of the signal. A NK1R antagonist Spantide (500 nM) blocked such substance-P derived change, suggesting the involvement of platelets in the action of substance-P. In contrast, substance-P did not increase the clot signal of platelet-containing but leukocyte-removed plasma. From these, we conclude that substance-P promotes platelet-dependent clot formation through NK1R, in which leukocytes appear to be involved.
Azma
Toshiharu
T
Department of Anesthesiology, Faculty of Medicine, Saitama Medical University, Iruma, Saitama, Japan. azmacci@nifty.com
Matsubara
Yuki
Y
Kinoshita
Hiroyuki
H
Hidaka
Ikuhiro
I
Shiraishi
Seiji
S
Nakao
Masakazu
M
Kawamoto
Masashi
M
Yuge
Osafumi
O
Hatano
Yoshio
Y
D001777:Blood Coagulation; D001780:Blood Coagulation Tests / Q000295:instrumentation; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D007692:Diatomaceous Earth / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000737:chemistry / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013373:Substance P / Q000502:physiology*; D019851:Thrombophilia / Q000097:blood*
D018040:Receptors, Neurokinin-1; D013373:Substance P; D007692:Diatomaceous Earth; D002118:Calcium