Conversion of dynorphin-(1-9) to [Leu5]enkephalin by the mouse vas deferens in vitro

The inhibitory action of dynorphin-(1-9) on the electrically stimulated mouse vas deferens was seen to be antagonised by the delta-selective opioid antagonist ICI 174864. The observed delta-receptor mediated responses were partially, but not totally, prevented by peptidase inhibitors which protect the C- and N-termini of dynorphin-(1-9). [3H]Dynorphin-(1-9) is rapidly degraded by slices of vasa deferentia of the mouse. The major product of this metabolism co-elutes with [Leu5]enkephalin on reverse phase HPLC. It is concluded that a major component of the inhibitory effects of dynorphin-(1-9) on the mouse vas deferens is mediated by degradation to [Leu5]enkephalin which in turn acts through delta-receptors. It is possible that in other in vitro and in vivo systems, the effects produced by dynorphin-(1-9) might be similarly mediated by delta-receptor activation.