Blockade of the antinociceptive effect of spinally administered kyotorphin by naltrindole in mice.

We investigated the role of spinal opioid receptors in the antinociceptive effect of kyotorphin (Tyr-Arg, KTP) by using an in vivo mice tail-pinch test and an in vitro opioid receptor binding assays. Intrathecal administration of KTP produced a dose-dependent antinociceptive effect with an ED(50) value of 24 microg/mouse. This antinociception, which was reversed by the KTP antagonist Leu-Arg, was completely blocked by naltrindole but not by naloxonazine, beta-funaltrexamine, or nor-binaltorphimine. The results from the binding study in vitro indicated that KTP bound to spinal KTP receptors but not to any opioid receptors in the mouse spinal cord. These results suggest that KTP-induced antinociception is mediated by binding to KTP receptors followed by an indirect activation of the delta-opioid receptors in the spinal cord.