Synergistic effect of epinephrine and shearing on platelet activation.
Platelet activation mediated through the interaction between von Willebrand factor (vWF) and platelet glycoprotein (GP) Ib is known to occur under high shear rate. We have demonstrated that low concentration of epinephrine could reduce the threshold level of shear rate necessary to cause platelet activation with purified system devoid of the effect of plasma proteins other than vWF. Both the extent of platelet aggregation and [Ca2+]i were continuously measured with optically modified cone-and-plate viscometer. No aggregation with no change in [Ca2+]i occurred under shear rate less than 7,200 s-1 in the absence of exogeneously added epinephrine. Epinephrine enhanced platelet aggregation under moderate level of shear rate (7,200 s-1) in a dose dependent manner. Significant aggregation with rise in [Ca2+]i was demonstrated even under the low shear rate of 1,200 s-1 when exogeneously added low concentration of epinephrine (0.05 microM) which did not cause platelet activation by itself was present. Aggregation and rise in [Ca2+]i under low shear in the presence of epinephrine was abolished by monoclonal antibodies against A1 domain of vWF or GP Ib, like aggregation and the rise in [Ca2+]i occurred under high shear rate (10,800 s-1), alpha 2-receptor blockade yohimbine completely antagonized the enhancing effects of epinephrine. Our findings suggested that epinephrine and shearing synergistically activated platelets through vWF interaction to GP Ib, which might suggest the role of sympathetic stimulation for the onset of acute arterial thrombosis.
Goto
S
S
First Dept. Intern. Med., Tokai Univ. School of Med., Isehara, Japan. shinichi@is.icc.u-tokai.ac.jp
Handa
S
S
Takahashi
E
E
Abe
S
S
Handa
M
M
Ikeda
Y
Y
D001809:Blood Viscosity; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D012212:Rheology; D015016:Yohimbine / Q000494:pharmacology; D014841:von Willebrand Factor / Q000276:immunology / Q000378:metabolism
D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D015016:Yohimbine; D002118:Calcium; D004837:Epinephrine