NEP/CALLA or CD10 is an endopeptidase (E.C. 188.8.131.52) that inactivates numerous neuropeptides, including dynorphin. Dynorphin is an endogenous opioid polypeptide that binds to kappa-opioid receptors with greatest affinity. R1.1 mouse thymoma cells highly express kappa-opioid receptors. In this study, on R1.1 cells, NEP activity was inhibited by kappa-opioid polypeptide dynorphin (10(-8)-10(-6) M) and by thiorphan (2 x 10(-4) M), a known inhibitor of NEP (30 min treatment). NEP inhibition by dynorphin was stronger than by thiorphan. A non-opioid opioid mechanism of action was mostly involved in this inhibition.