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Differences in Binding Properties of μ and δ Opioid Receptor Subtypes from Rat Brain: Kinetic Analysis and Effects of Ions and Nucleotides
Author(s) -
Zajac JeanMarie,
Roques Bernard P.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb08802.x
Subject(s) - nucleotide , chemistry , kinetic energy , biophysics , opioid receptor , ion , receptor , opioid , neuroscience , pharmacology , biochemistry , biology , gene , physics , organic chemistry , quantum mechanics
Differences in binding properties of μ and δ opioid receptors were investigated using DAGO (Tyr‐ d ‐Ala‐Gly‐MePhe‐Gly‐ol) and DTLET (Tyr‐ d ‐Thr‐Gly‐Phe‐Leu‐Thr), which occur, respectively, as the most selective μ and δ radioligands available. At high concentration, each agonist is able to interact with its nonspecific sites. Competition experiments indicated that a two‐site competitive model was adequate to explain the interactions of DAGO and DTLET with [ 3 H]DTLET and [ 3 H]DAGO binding sites, respectively. The weak cross‐reactivity (≃10%) of DTLET for μ sites was taken into account in these experiments. On the other hand, DAGO and DTLET exhibit differential binding kinetics. Thus, at 35°C, the lifetime of DTLET within its receptor site about 14 times longer than that of the μ agonist. Sodium and manganese ions decrease the maximal number of high affinity μ and δ sites, but the sensitivity of μ receptors is three times higher towards Na + and 20‐fold higher towards Mn 2+ than that of δ receptors. GTP reduces similarly the μ and δ binding whereas only the DAGO binding was modified by the nonhydrolyzable analogue guanylylimidodiphosphate [GMP‐P(NH)P]. However, in the presence of Na + ions, GMP‐P(NH)P inhibits the DTLET binding in a concentration‐dependent manner. The effects of Na + and GMP‐P(NH)P could be explained by a sequential transformation of δ receptors to low‐affinity states. This model predicts that Na + , by lowering the affinity of a fraction of sites, produces a decrease in the maximal number of high‐affinity δ receptors and that GMP‐P(NH)P enhances the Na + , effect. Moreover, the binding kinetic to this high‐affinity state was also modified by Na + and nucleotides. All of these data support the existence of two independent μ and δ binding sites, the properties of which are differentially regulated by these endogenous effectors.