title: Interaction of opiates with opioid binding sites in the bovine adrenal medulla: II. Interaction with kappa sites.
abstract: In this study we examined the interaction of opiates with kappa binding sites in the bovine adrenal medulla. [3H]Ethylketocyclazocine (EKC), [3H]etorphine, and [3H]bremazocine stereoselective bindings were used to assay these interactions. The kappa sites were found to be heterogeneous: [3H]bremazocine identified with high affinity all subtypes of these sites. [3H]EKC, in the presence of saturating concentrations of [D-Ala2, D-Leu5]-enkephalin (DADLE) (5 microM), was used to identify kappa 1 sites, on which dynorphin A (1-13) bound with high affinity. Either [3H]EKC or [3H]etorphine in the presence of 5 microM DADLE identified the kappa 2 subtype. This subtype was found to interact with beta-endorphin and especially with the octapeptide Met5-enkephalyl-Arg6-Gly7-Leu8. Furthermore, [3H]etorphine identified in the bovine adrenal medulla a third high-affinity component, in the presence of 5 microM DADLE. This residual interaction was found to be equally stereoselective and presenting kappa selectivity. Met5-enkephalyl-Arg6-Phe7 interacted preferentially with this site. The three kappa subtypes interacted differentially with monovalent (Na+, K+, and Li+) and divalent (Ca2+, Mg2+, and Mn2+) ions by modification of the apparent concentration of the accessible sites and/or by changes of the apparent KD for radioligands. Modifying agents (proteolytic enzymes, thiol-modifying reagents, and A2-phospholipase) produced different effects on each subtype of the kappa site, suggesting a different protein (or protein-lipid?) composition.
authors.forename: E
authors.initials: E
authors.lastname: Castanas
authors.forename: N
authors.initials: N
authors.lastname: Bourhim
authors.forename: P
authors.initials: P
authors.lastname: Giraud
authors.forename: F
authors.initials: F
authors.lastname: Boudouresque
authors.forename: P
authors.initials: P
authors.lastname: Cantau
authors.forename: C
authors.initials: C
authors.lastname: Oliver
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D001575:Benzomorphans / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004744:Enkephalin, Methionine / Q000378:metabolism; D016314:Ethylketocyclazocine; D005033:Ethylmaleimide / Q000494:pharmacology; D005048:Etorphine / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010741:Phospholipases A / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D012964:Sodium / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D001575:Benzomorphans; D004723:Endorphins; D009294:Narcotics; D009842:Oligopeptides; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D005048:Etorphine; D008345:Manganese; D004744:Enkephalin, Methionine; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; C028889:morphiceptin; D008094:Lithium; D012964:Sodium; D010741:Phospholipases A; C027248:bremazocine; D003496:Cyclazocine; D005033:Ethylmaleimide; D011188:Potassium; D002118:Calcium