DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

850
Endothelial cells
Platelets
+
COX-1
IIa
PAR1/PAR4
COX-1
GPIIb/IIIa
TxA 2
PGI 2
GPIIb/IIIa
Fibrinogen
P2Y 1 /P2Y 12
ADP
SECTION III
MODULATION OF CARDIOVASCULAR FUNCTION
GPIa/IIa
Collagen
Smooth muscle cells/macrophages
GPIb
vWF
Figure 30–1. Platelet adhesion and aggregation. GPIa/IIa and GPIb are platelet receptors that bind to collagen and von Willebrand factor
(vWF), causing platelets to adhere to the subendothelium of a damaged blood vessel. PAR1 and PAR4 are protease-activated receptors that
respond to thrombin (IIa); P2Y 1
and P2Y 12
are receptors for ADP; when stimulated by agonists, these receptors activate the fibrinogenbinding
protein GPIIb/IIIa and cyclooxygenase-1 (COX-1) to promote platelet aggregation and secretion. Thromboxane A 2
(TxA 2
) is the
major product of COX-1 involved in platelet activation. Prostaglandin I 2
(prostacyclin, PGI 2
), synthesized by endothelial cells, inhibits platelet
activation.
Endothelial cells
Platelets
X
IX
X
IXa
VIIIa
Xa
Va
II
Fibrinogen
TF
TF
TF
VIIa
TF
TF
IIa
TF
Fibrin
TF
TF
Smooth muscle cells/macrophages
Figure 30–2. Major reactions of blood coagulation. Shown are interactions among proteins of the “extrinsic” (tissue factor and factor VII),
“intrinsic” (factors IX and VIII), and “common” (factors X, V, and II) coagulation pathways that are important in vivo. Boxes enclose the
coagulation factor zymogens (indicated by Roman numerals); the rounded boxes represent the active proteases. TF, tissue factor. Activated
coagulation factors are followed by the letter “a”: II, prothrombin; IIa, thrombin.