Fig. 8: Inhibition of CAP-induced TRPV1 activation by exendin 9–39 fragments and the analgesic effects of exendin 20–29 on CAP-induced nociceptive behaviors in mice. | Experimental & Molecular Medicine

Fig. 8: Inhibition of CAP-induced TRPV1 activation by exendin 9–39 fragments and the analgesic effects of exendin 20–29 on CAP-induced nociceptive behaviors in mice.

From: GLP-1 and its derived peptides mediate pain relief through direct TRPV1 inhibition without affecting thermoregulation

Fig. 8

a Sequence alignment of three truncated small peptides derived from exendin 9–39, their overlapping sequence exendin 20–29, and the molecular weights of these peptides. b Mean normalized calcium influx in CHO K1 cells expressing human TRPV1 with control CAP (100 nM) and each of the four truncated small peptides derived from exendin 9–39 (100 nM each) (mean ± S.E.M.). One-way ANOVA followed by Dunnett’s multiple comparison test (****p < 0.0001, compared with the control, CAP). c Mean normalized currents of sequential CAP-induced currents (mean ± S.E.M.). One-way ANOVA followed by Dunnett’s multiple comparison test (****p < 0.0001, compared with the control, CAP). d Effects of intraplantar administration of exendin 20–29 (20 μg) and BCTC (0.5 μg) on CAP (1.6 μg)-induced acute licking time (mean ± S.E.M., n = 6). One-way ANOVA followed by Dunnett’s multiple comparison test (##p < 0.01, compared with the vehicle + CAP group). e Effects of intraplantar administration of exendin 20–29 (20 μg) on CAP-induced acute thermal hyperalgesia (left) and mechanical allodynia (right) in mice. Two-way ANOVA followed by the Bonferroni multiple comparison test (*p < 0.05, vehicle + CAP group compared with the exendin 20–29 [20 μg] group; #p < 0.05, ##p < 0.01, vehicle + CAP group compared with the BCTC [0.5 μg] + CAP) group. f Effects of the intraperitoneal administration of 10 μg/kg exendin 20–29 or 10 μg/kg exendin-4 on blood glucose levels following the administration of 2 g/kg glucose (mean ± S.E.M., n = 5). Two-way ANOVA followed by the Bonferroni multiple comparison test (**p < 0.01, ****p < 0.0001, compared with the vehicle group; ##p < 0.01, ####p < 0.0001, compared with the glucose control group; †p < 0.05, ††††p < 0.0001, compared with the exendin-4 group). g Schematic illustration of the potential mechanism by which exendin 20–29 does not disrupt the regulation of blood glucose levels in the pancreas, where GLP-1 receptors are present. ANOVA analysis of variance, BCTC N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide, CAP capsaicin, CHO K1 Chinese hamster ovary, GLP-1 glucagon-like peptide-1, S.E.M. standard error of the mean, TRPV1 transient receptor potential vanilloid 1.

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