Opioid ligand binding sites in the spinal cord of the guinea-pig.
The properties of opioid binding sites in membranes from the spinal cord of the guinea-pig were analyzed in experiments employing radiolabeled opioid ligands, selective or partially selective for mu, delta and kappa-type binding sites. Incubation was conducted at 37 degrees C in a quasi-physiological modified Krebs medium, containing sodium and magnesium. The types of binding sites were discriminated on the basis of their affinities for [3H-D-Ala2-MePhe4-Gly5-ol]enkephalin ([3H]DAGO), [3H-D-Ala2-D-Leu5]enkephalin, and [3H]ethylketocyclazocine and the relative potencies of the displacing ligands, DAGO, [D-Ser2-Leu5]enkephalyl-Thr and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide methanesulfonate hydrate (U50488H), which are selective for mu, delta and kappa type binding sites respectively. In membranes from whole spinal cord, kappa type sites comprised about 60%, mu about 30% and delta about 10% of the total of mu, delta and kappa binding sites. Binding sites of the mu type were also found in the lumbo-sacral region of guinea-pig spinal cord, in contrast to earlier reports of their absence from this tissue. Morphine showed a better than 500-fold selectivity for mu over kappa sites in spinal cord, while nalbuphine and (-)1-cyclopentyl-5-(1,2,3,4,5,6-hexahydro-8-hydroxy-3,6,11- trimethyl-2,6-methano-3-benzazocin-11-yl)3-pentanone methanesulfonate (WIN 44441-3) showed about a 10-fold selectivity for mu sites. The drug U50488H had about a 150-fold greater affinity for kappa than mu-type binding sites.
D000818:Animals; D001667:Binding, Competitive; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000378:metabolism; D016314:Ethylketocyclazocine; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013116:Spinal Cord / Q000378:metabolism*
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D003496:Cyclazocine