Postnatal development of delta-opioid receptor subtypes in mice

1 The density and affinity of binding sites for the delta-selective opioid ligands [H-3]-[D-Ala(2), Asp(4)]deltorphin (DELT-I), [H-3]-[D-Ala(2)Glu(4)]-deltorphin (DELT-II), [H-3]-[D-Pen(2),D-Pen(5)]enkephalin (DPDPE), and [H-3]-naltrindole (NTI) were determined in whole brain from 10, 15, 25 and 60 day-old C57BL mice. 2 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 [H-3]-NTI was about one half that labelled by [H-3]-DELT-I, [H-3]-DELT-II and [H-3]-DPDPE. In 25 and 60 day-old mouse brain the DPDPE B-max was 25% less than the deltorphin-II B-max. 3 In saturation experiments, specific binding of [H-3]-DELT-I on adult mouse brain homogenates was best fitted by a two-site model (34% high affinity site, K-d=1.08 nM and 66% low affinity sites, K-d=39.9 nM). 4 DPDPE produced a biphasic inhibition of specific [H-3]-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. 5 In adult mouse brain labelled with [H-3]-DELT-I, DELT-II recognized 71% of high-affinity and 29% of low-affinity sites. DELT-I and DPDPE produced monophasic inhibition of specific [H-3]-DELT-II binding to brain homogenates of adult mice. 6 These data suggest that a sub-population of delta-sites (probably the delta(2)-subtype), recognized by DELT-I, with high affinity for DELT-II and low affinity for DPDPE develops from 25 days onward. 7 In electrically stimulated mouse vas deferens (MVD) the rank order of potency of the three delta-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 delta(2)-subtype.