Ontogeny of mu and delta opioid receptors and of neutral endopeptidase in human spinal cord: an autoradiographic study.

The distributions of the neutral endopeptidase 24.11 (NEP; enkephalinase) and of mu and delta opioid receptors have been studied by autoradiography in the human spinal cord during ontogenesis, mu and delta sites were assessed by using [3H]DAGO and [3H]DTLET respectively and NEP was labelled by [3H]HACBO-Gly, a NEP inhibitor. Labelling by the three markers was found at an early stage of development of the central nervous system (14 weeks) and was mainly localized in the gray matter, with highest densities in the superficial layers of the dorsal horn. Moreover [3H]DAGO also diffusely labelled the ventral motor areas. NEP and delta binding sites were localized transiently in the fasciculus gracilis at the cervical level at a fetal age of 24 weeks, an area where no enkephalin-like immunoreactivity (ELI) has been found. Conversely no opioid binding sites or NEP were observed at a fetal age of 18 weeks in the intermediolateral region where ELI fibres and cells were detected transiently. In general, a better correlation between the distribution of NEP and that of delta opioid sites was observed. Meninges contained a very high density of [3H]HACBO-Gly sites. This labelling appeared almost simultaneously with that in the spinal cord tissue and increased with maturation. An increase in labelling by the three markers appeared slightly earlier than the clustering of ELI fibres in the substantia gelatinosa. Our data show that in the human spinal cord, structural and biochemical elements involved in enkephalinergic transmission appear almost simultaneously and early in ontogeny.