Endogenous ligands for kappa-opiate receptors.
The receptor preferences of opioids in the mouse vas deferens was tested by means of tolerance and cross-tolerance studies. The preparations were rendered tolerant in situ by superfusion with the kappa-receptor agonist dynorphin and with alpha-neoendorphin, respectively, and set up in vitro in the presence of the respective peptide to maintain tolerance. The investigations revealed strong kappa-agonistic activities both of alpha-neoendorphin and of dynorphin and its fragments 1-13 and 1-11. As the dynorphin chain shortened, the kappa-receptor activity declined and delta-receptor activity became progressively apparent. Interestingly, the octapeptide met-enkephalin[Arg6,Gly7,Leu8], a fragment of the adrenal medulla proenkephalin, also displayed considerable kappa-agonistic properties under the experimental conditions employed. Presumably, the decapeptide alpha-neoendorphin and the octapeptide met-enkephalin[Arg6,Gly7,Leu8] cover in addition to the kappa-receptor population in the MVD further opiate receptors, most probably delta-receptors.