Interaction of selective mu and delta ligands with the kappa 2 subtype of opiate binding sites

In the lumbo-sacral spinal cord of rat and guinea-pig 3H-etorphine selectively interacts with the kappa 2 subtype whose binding properties are distinct from those of mu, delta and kappa sites. The affinity of some mu (DAGO, morphiceptin, morphine) and delta (DADLE, DSTLE) ligands for this site are ranging from 40 to 2000nM, suggesting their significant cross-reactivity with this kappa 2 subtype. The saturation curves of 3H-etorphine in the presence of morphiceptin (2 or 10 microM) or DAGO (0.1 or 0.2 microM) or DSTLE (0.1 microM) reveal an affinity decrease without any change of the binding capacity. The KI values extrapolated from the double-reciprocal plots are similar to those calculated from the monophasic displacement curves. These results can be interpreted only in terms of a competitive-type interaction with a single class of kappa 2 sites and confirms the absence of mu and delta sites in the lumbo-sacral spinal cord of both species.