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 beta-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 microg/kg) dose- and time-dependently induced potent analgesic effect (ED(50)=3.22 microg/kg). This effect was fully blocked by naloxone and significantly inhibited by co-injection (i.c.v.) with beta-funaltrexamine or naltrindole, but not by nor-binaltorphimine, indicating the involvement of both mu- and delta-opioid receptors in the analgesic response evoked by opiorphin. In addition, i.c.v. administration of 5 microg/kg opiorphin produced the comparative effect as 10 microg/kg morphine on the analgesia, suggesting that opiorphin displayed more potent analgesic effect than that induced by morphine.