Agonist- and Ca2+-dependent Desensitization of TRPV1 Channel Targets the Receptor to Lysosomes for Degradation

Abstract

Background:The contribution of TRPV1 trafficking to vanilloid-induced desensitization and tachyphylaxis remains unexplored. Results: Agonist exposure promotes TRPV1 internalization and degradation in nociceptors and HEK293 cells, in a time-, dose-, and Ca 2ϩ -dependent manner. Conclusion: Agonist-induced TRPV1 internalization and degradation notably contribute to long-term nociceptor desensitization. Significance: Modulation of surface TRPV1 levels could be a therapeutic approach for pain treatment.

Cardiac sympathetic afferent stimulation induces salt-sensitive sympathoexcitation through hypothalamic epithelial Na+ channel activation

“…In the present study, we performed chemical CSA stimulation with a slightly higher dose of capsaicin than typically used in other studies since the capsaicin-containing filter paper was kept on the surface of the LV wall for several days, which raised a concern about CSA desensitization (22,26). When capsaicin was used to ablate the sensory nerve, the dose of capsaicin was significantly higher than that in the present study (22,26). The reproducibility of acute AP elevation in response to the epicardial application of capsaicin to negate the possibility of the sensory nerve ablation could be confirmed.…”

Potentiation of the Transient Receptor Potential Vanilloid 1 Channel Contributes to Pruritogenesis in a Rat Model of Liver Disease

“…Biotin Labeling of Surface TRPV1 and PAR 2 Proteins-Dissociated DRG neurons from sham-and BDL-operated rats were surface biotinylated with sulfo-NHS-SS-Biotin (Pierce) and processed as described (33). Biotinylated proteins were isolated with streptavidin-agarose, resolved by SDS-PAGE, and detected with the following antibodies and dilutions: TRPV1 (1:1000), PAR 2 (1:100), and ␤-actin (1:200).…”

“…Besides histamine and endogenous opioids (33), also tryptase, chimase, and other proteases are released during inflammation by immune cells (34). To assess the involvement of proteases in the scratching behavior, we administered the specific lima bean trypsin inhibitor, the serine protease inhibitor gabexate mesylate, and the PAR 2 receptor antagonist, FSLLRY-NH 2 into BDL-and sham-operated rats.…”

Can Capsaicin Present in Food Act as Carcinogenic, Antitumor or Both

“…After this dose of capsaicin, the response was stabilized with a slight decline in the concentration of intracellular calcium, but this effect could be blocked (capsazepine 1 µM inhibit the binding of capsaicin 5 µM) [41]. Other two agonists (resiniferatoxin and (R)-methanandamide), at high doses, were neither able to induce an increase in [Ca2+]i, suggesting that the mechanism of cell death probably occurs via TRPV1 [42].…”

“…Depending on the vanilloid, dose, concentration and administration site, nociceptor refractoriness may last from minutes to months, suggesting the contribution of different cellular mechanisms. So, it can explain the paradoxal use of capsaicin as an analgesic agent to treat different pain disorders [26]. It was also observed that capsaicin can lead the local cells to death and induce DNA fragmentation in a concen-tration-dependent manner [12,27,28].…”