Abstract

The effects of dehydroepiandrosterone (5-androsten-3β-ol-17-one; DHEA) and related steroids on the capsaicin receptor-mediated current were studied in acutely dissociated rat dorsal root ganglion neurons using the whole-cell voltage-clamp technique. DHEA rapidly and reversibly inhibited the capsaicin-induced current in a concentration-dependent manner, with an EC₅₀ of 6.7 μM and a maximal inhibition of 100%. DHEA increased the capsaicin EC₅₀ with little effect on the capsaicin maximal response, suggesting that the blocking action of DHEA is competitive. Neither the capsaicin response nor inhibition of the capsaicin response by extracellularly applied DHEA was significantly affected by inclusion of a saturating concentration of DHEA in the electrode buffer, arguing that DHEA acted at the extracellular surface of the membrane. Moreover, DHEA did not act through protein phosphatases to inhibit the capsaicin-induced current. Furthermore, the stereoisomer of DHEA, 5-androsten-3α-ol-17-one, failed to inhibit the capsaicin-induced current, producing instead a potentiating effect on the capsaicin response, demonstrating that the interaction of steroids with the capsaicin receptor is stereospecific. The inhibitory action of DHEA on the capsaicin-induced current may provide a basis for reducing capsaicin receptor-mediated nociception.