OBJECTIVE: Melittin (MEL) is a major component of bee venom and can produce both persistent spontaneous nociception and pain hypersensitivity when injected subcutaneously in the periphery. The present study aimed to examine the roles of transient receptor potential canonical (TRPC) channels in mediation of MEL-induced activation of primary nociceptive cells. METHODS: Whole-cell patch-clamp and laser scanning confocal calcium detection were used to evaluate the effects of SKF-96365, a TRPC inhibitor, applied on the acutely isolated dorsal root ganglion (DRG) cells of rat, on MEL-induced increase in intracellular calcium concentration ([Ca(2+)](i)) and inward current. RESULTS: Under voltage-clamp mode, 43.9% (40/91) DRG cells were evoked to give rise to the inward current by 2 μmol/L MEL, which could be significantly suppressed by 3 doses of SKF-96365 (1, 5 and 10 μmol/L) in a dose-dependent manner. Of the other 210 cells, 67.6% responded to MEL with an intracellular Ca(2+) rise, as revealed by confocal calcium imaging. Of these MEL-sensitive cells, 46.5% (66/142) were suppressed by the highest dose of SKF-96365. CONCLUSION: MEL-induced activation of small to medium-sized DRG cells can be suppressed by SKF-96365, suggesting the involvement of TRPC channels in the mediation of MEL-induced activation of primary nociceptive cells.
OBJECTIVE: Melittin (MEL) is a major component of bee venom and can produce both persistent spontaneous nociception and painhypersensitivity when injected subcutaneously in the periphery. The present study aimed to examine the roles of transient receptor potential canonical (TRPC) channels in mediation of MEL-induced activation of primary nociceptive cells. METHODS: Whole-cell patch-clamp and laser scanning confocal calcium detection were used to evaluate the effects of SKF-96365, a TRPC inhibitor, applied on the acutely isolated dorsal root ganglion (DRG) cells of rat, on MEL-induced increase in intracellular calcium concentration ([Ca(2+)](i)) and inward current. RESULTS: Under voltage-clamp mode, 43.9% (40/91) DRG cells were evoked to give rise to the inward current by 2 μmol/L MEL, which could be significantly suppressed by 3 doses of SKF-96365 (1, 5 and 10 μmol/L) in a dose-dependent manner. Of the other 210 cells, 67.6% responded to MEL with an intracellular Ca(2+) rise, as revealed by confocal calcium imaging. Of these MEL-sensitive cells, 46.5% (66/142) were suppressed by the highest dose of SKF-96365. CONCLUSION: MEL-induced activation of small to medium-sized DRG cells can be suppressed by SKF-96365, suggesting the involvement of TRPC channels in the mediation of MEL-induced activation of primary nociceptive cells.
Authors: Antonio Riccio; Andrew D Medhurst; Cesar Mattei; Rosemary E Kelsell; Andrew R Calver; Andrew D Randall; Christopher D Benham; Menelas N Pangalos Journal: Brain Res Mol Brain Res Date: 2002-12-30
Authors: Manuela B Pucca; Felipe A Cerni; Isadora S Oliveira; Timothy P Jenkins; Lídia Argemí; Christoffer V Sørensen; Shirin Ahmadi; José E Barbosa; Andreas H Laustsen Journal: Front Immunol Date: 2019-09-06 Impact factor: 7.561