Fig. 8.
Exendin-4 (Ex-4) induced substance P (SP) release from dorsal root ganglia (DRG) neurons occurs in sensory neurons that express transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) channels. DRG from TRPV1 knockout (KO) (A) and TRPA1 KO (B) animals were cocultured with SP sensors (gray bars) and exposed to 50 nM Ex-4, followed by capsaicin (Cap), allyl isothiocyanate (AITC), and KCl. Concentrations of the treatments were as described in Fig. 6. A: TRPV1 KO neurons (black bars) produce a significant increase in Ex-4 calcium response and also a corresponding SP-sensor (gray bars) response. Cap treatment, however, does not result in significant difference in either DRG neurons or SP-sensor intracellular calcium concentration ([Ca2+]i). Attenuation in the transient increase in the [Ca2+]i of DRG neurons calcium, but not in SP, is observed with AITC treatment. B: TRPA1 KO neurons (black bars) also show a transient increase in the [Ca2+]i in response to Ex-4 which corresponds to SP secretion (gray bars). Greater than 400 neurons were examined in 3 independent cultures from 3 mice for each genotype. Bars are means ± SE (n = 3 animals). NFR, normalized fura-2 AM response; NS, not significant. *P < 0.05, ***P < 0.001. Statistical analysis was by ANOVA using Tukey's post hoc test.