Evidence for multiple "Kappa" binding sites by use of opioid peptides in the guinea-pig lumbo-sacral spinal cord.
Binding properties of [3H]-etorphine and [3H]-ethylketocyclazocine have been studied in the lumbo-sacral spinal cord of guinea-pig which does not contain mu or delta binding sites. [3H]-etorphine binds to a single class of high affinity sites, whereas [3H]-ethylketocyclazocine interacts with a high and a low affinity component. Using a discriminative procedure, 5 microM (D-Ala2, D-Leu5) enkephalin (DAL), the high affinity component of [3H]-ethylketocyclazocine can be resolved in two classes of sites, (D-Ala2, D-Leu5) enkephalin sensitive sites (DALS sites) and (D-Ala2, D-Leu5) enkephalin insensitive sites (DALI sites). In these conditions, there is a total loss of [3H]-etorphine sites, whose binding capacity and properties strictly correspond to the DALS sites labelled by [3H]-ethylketocyclazocine. Pharmacological investigations indicate that DALI sites for which dynorphin (1 leads to 17) is the best ligand, can be related to kappa sites previously described in guinea-pig brain, whereas DALS sites for which (Arg6, Phe7) Met-enkephalin possesses a good affinity, closely correspond to benzomorphan sites recently characterized in rat brain and spinal cord. [3H]-ethylketocyclazocine interacts additionally with "non opiate" low affinity sites, for which only benzomorphan drugs exhibit a good affinity, whereas morphine, naloxone, phencyclidine or endogenous opioid peptides do not present any affinity for them. On the basis of these data, a new subdivision of "kappa" sites is discussed.
D000818:Animals; D001665:Binding Sites; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D016314:Ethylketocyclazocine; D005048:Etorphine / Q000378:metabolism; D006168:Guinea Pigs; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D013116:Spinal Cord / Q000378:metabolism*
D004723:Endorphins; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D005048:Etorphine; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D004090:Dihydromorphine; D003496:Cyclazocine