Thrombin and PAR1-activating peptide: effects on human uterine contractility in vitro

Modulation of human uterine smooth muscle cell collagen contractility by thrombin, Y-27632, TNF alpha and indomethacin

“…It had previously been established that thrombin enhanced myometrial contractions in human and animal myometrium [ 10 , 29 , 30 ]. We reported the up-regulation in gene expression of two of its cellular receptors, F2R and F2RL3 at labour [ 12 ].…”

Corneal Activation of Prothrombin to Form Thrombin, Independent of Vascular Injury

“…Examples of PAR-regulated processes that occur without injury include renal hemodynamics, ion transport across intestinal cells, normal contraction and relaxation of smooth muscle cells of the gut and airways, uterine contraction, calcium signaling in cells including neurons and astrocytes, and release of cytokines and chemokines by lung epithelial and fibroblast cells, microglial cells, and corneal epithelial, stromal, and endothelial cells. 7,9,[65][66][67][68][69] Before the current characterization of the corneal system, synthesis of components of the coagulation cascades was reported in some vascularized tissues. Prothrombin and its mRNA were found in the brain cortex, cerebella, hippocampus, muscle, and kidney.…”

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“…The possibility that the vasodilatory effect of thrombin may serve to counteract the diminished perfusion associated with the pathophysiology of these conditions, at least in the early stages of disease, is one hypothesis. A further theory is that the much enhanced uterine contractility elicited by thrombin and PAR1-AP [13] may be concomitantly associated with a feto-placental vasodilatory effect to maintain good utero-placental blood flow.…”

“…PAR activation has been closely linked to inflammation [6,8], contraction of vascular [5] and non-vascular [9,10] smooth muscle, and platelet activation [6]. Although PAR-1, PAR-3 and PAR-4 [11] are all known to be thrombin receptors, the mechanism of activation by thrombin at these different PARs varies [12,13]. …”