Anti-analgesic activity of enterostatin (VPDPR) is mediated by corticosterone.

Although enterostatin (VPDPR) inhibited morphine-induced analgesia, it had no affinity for mu-opioid receptors. VPDPR administration was reported to elevate serum corticosterone levels. We found that corticosterone exhibited a similar anti-analgesic effect selective for mu-opioid. Furthermore, the anti-analgesic effect of VPDPR was inhibited by RU486, an antagonist for the glucocorticoid receptor. The anti-analgesic effect of VPDPR was not observed in adrenalectomized mice. These results suggest that the anti-analgesic activity of VPDPR is mediated by corticosterone released from the adrenal cortex.