[Description]:
TFLLR-NH2 is a selective PAR1 agonist with an EC50 of 1.9 μM.
[Related Catalog]:
[Target]
[In Vitro]
PAR1 agonists stimulate concentration-dependent increases in [Ca2+]i and in the proportions of neurones. The maximal increase in [Ca2+]i above basal is detected in response to 10 μm TF-NH2(peak 196.5±20.4 nM, n=25) when 50–80% of identified neurones responded[1]. SW620 cells cultured in the supernatant of TFLLR-NH2-activated platelets upregulate E-cadherin expression and downregulate the vimentin expression. In the in vitro platelet culture system, a TFLLR-NH2 dose-dependent increase of secreted TGF-β1 is detected in the supernatant[2].
[In Vivo]
Injection of TF-NH2 into the rat paw stimulates a marked and sustained oedema. An NK1R antagonist and ablation of sensory nerves with capsaicin inhibit oedema by 44% at 1 h and completely by 5 h. In wild-type but not PAR1−/− mice, TF-NH2 stimulates Evans blue extravasation in the bladder, oesophagus, stomach, intestine and pancreas by 2–8 fold. Extravasation in the bladder, oesophagus and stomach is abolished by an NK1R antagonist[1]. TFp-NH2 produces notable contraction at 3-50 μM and relaxation at 0.3-50 μM, in the absence of apamin. The concentration-response curve for TFp-NH2-induced contraction is remarkably shifted left, when the TFp-NH2-induced relaxation is blocked by apamin at 0.1 μM[3].
[Animal admin]
Mice: Mice are anaesthetized with isofluorane, and saline or TF-NH2 (3 μmol/kg in 25 μL physiological saline) is injected into the lateral tail vein. Evans blue (33.3 mg/kg in 50 μL saline) is co-injected with the peptide. Mice are perfused transcardially at 10 min after administration of TF-NH2 with physiological saline containing 20 u/mL heparin at a pressure of 80-100 mmHg for 2-3 min. Excised tissues are incubated in 1 mL of formamide for 48 h, and Evans blue content is measured spectrophotometrically at 650 nm[1].
[References]
[Related Small Molecules]