Evidence for δ‐Opioid Binding and GTP‐Regulatory Proteins in 5‐Day‐Old Rat Brain Membranes

Maria Szücs, Carmine J. Coscia

Research output: Article

21 Citations (Scopus)

Abstract

The availability of the bispenicillamine enkephalin [3H][d‐Pen2,d‐Pen5]enkephalin ([3H]DPDPE) a highly selective ligand for δ‐opioid receptors, has made possible a more definitive examination of the ontogeny of this receptor subtype. In this report, the binding characteristics of [3H]DPDPE in 5‐day‐old neonatal (P‐5) and adult rat brain are compared. Analysis of saturation curves as well as homologous displacement data revealed no significant difference in the binding affinity of [3H]DPDPE between P‐5 animals and adults. Conversely, the binding capacity increased fivefold during this period. The δ‐specificity of the sites was further proven by competition experiments with μ‐ and δ‐selective ligands. Mn2+ (0.5 mM) elevated [3H]DPDPE specific binding by lowering the Kd, whereas 50 μM 5′‐guanylylimidodiphosphate inhibited it by decreasing the total number of high‐affinity binding sites in both P‐5 animals and adults. Pertussis toxincatalyzed ADP ribosylation experiments revealed the presence of 40‐kDa proteins, with a molecular mass corresponding to G protein subunits αio, as early as 1 h after birth. There was a low, but detectable, basal low‐Km GTPase activity in P‐5 animals, which increased fivefold during postnatal development. The present report establishes the existence of high‐affinity [3H]DPDPE binding as well as GTP‐regulatory proteins 5 days after birth. Yet, heterologous competition studies and ionic effects suggest that neonatal binding sites differ from adult receptors. Whether the neonatal sites are newly synthesized, incompletely processed sites or a developmentally programmed isoform remains to be determined.

Original languageEnglish
Pages (from-to)1419-1425
Number of pages7
JournalJournal of neurochemistry
Volume54
Issue number4
DOIs
Publication statusPublished - ápr. 1990

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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