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Postnatal development of δ‐opioid receptor subtypes in mice
Author(s) -
Negri L,
Severini C,
Lattanzi R,
Potenza R L,
Melchiorri P
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700990
Subject(s) - naltrindole , enkephalin , chemistry , medicine , endocrinology , receptor , binding site , opioid receptor , opioid , biology , biochemistry
The density and affinity of binding sites for the δ‐selective opioid ligands [ 3 H]‐[ d ‐Ala 2 , Asp 4 ]deltorphin (DELT‐I), [ 3 H]‐[ d ‐Ala 2 Glu 4 ]‐deltorphin (DELT‐II), [ 3 H]‐[ d ‐Pen 2 , d ‐Pen 5 ]enkephalin (DPDPE), and [ 3 H]‐naltrindole (NTI) were determined in whole brain from 10, 15, 25 and 60 day‐old C57BL mice. At all ages, the analyses of the homologous displacement curves, gave best fits to single rather than to multiple site models. The binding capacity (B max ) labelled by [ 3 H]‐NTI was about one half that labelled by [ 3 H]‐DELT‐I, [ 3 H]‐DELT‐II and [ 3 H]‐DPDPE. In 25 and 60 day‐old mouse brain the DPDPE B max was 25% less than the deltorphin‐II B max . In saturation experiments, specific binding of [ 3 H]‐DELT‐I on adult mouse brain homogenates was best fitted by a two‐site model (34% high affinity site, K d =1.08 n m and 66% low affinity sites, K d =39.9 n m ). DPDPE produced a biphasic inhibition of specific [ 3 H]‐DELTI‐I binding, from 15 days of age onwards. The relative percentage of high and low affinity sites was 72% and 28% in 15 day‐, 65% and 35% in 25 day‐ and 30% and 70% in 60 day‐old mice. In adult mouse brain labelled with [ 3 H]‐DELT‐I, DELT‐II recognized 71% of high‐affinity and 29% of low‐affinity sites. DELT‐I and DPDPE produced monophasic inhibition of specific [ 3 H]‐DELT‐II binding to brain homogenates of adult mice. These data suggest that a sub‐population of δ‐sites (probably the δ 2 ‐subtype), recognized by DELT‐I, with high affinity for DELT‐II and low affinity for DPDPE develops from 25 days onward. In electrically stimulated mouse vas deferens (MVD) the rank order of potency of the three δ‐agonists was: DELT‐I> DELT‐II> DPDPE in 10 day‐old mice, and: DELT‐I= DELT‐II> DPDPE, from 25 days onward. During this time, the potency of DELT‐II increased about 15 fold whereas the potency of DELT‐I and DPDPE increased only 5 times. The higher efficacy of DELT‐II could depend on receptor maturation towards the δ 2 ‐subtype.British Journal of Pharmacology (1997) 120 , 989–994; doi: 10.1038/sj.bjp.0700990