TFLLR-NH2(TFA)

PAR1 agonists stimulate concentration-dependent increases in [Ca ²⁺ ]i and in the proportions of neurones. The maximal increase in [Ca ²⁺ ] 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. 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.

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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. 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.