Effects and underlying mechanisms of human opiorphin on colonic motility and nociception in mice

In the present study, we investigated the effects of human opiorphin on colonic motility and nociception in mice. In in vitro bioassay, opiorphin (10−6 to 10−4 M) caused colonic contraction in a concentration-dependent manner, which was completely blocked by naloxone and partially attenuated by β-funaltrexamine and naltrindole. Moreover, opiorphin (10−4 M) significantly enhanced the contractile response induced by Met-enkephalin. The data suggested that the effect of opiorphin on colonic contraction may be due to the protection of enkephalins. In in vivo bioassay, intracerebroventricular (i.c.v.) administration of opiorphin (1.25–10 μg/kg) dose- and time-dependently induced potent analgesic effect (ED50 = 3.22 μg/kg). This effect was fully blocked by naloxone and significantly inhibited by co-injection (i.c.v.) with β-funaltrexamine or naltrindole, but not by nor-binaltorphimine, indicating the involvement of both μ- and δ-opioid receptors in the analgesic response evoked by opiorphin. In addition, i.c.v. administration of 5 μg/kg opiorphin produced the comparative effect as 10 μg/kg morphine on the analgesia, suggesting that opiorphin displayed more potent analgesic effect than that induced by morphine.