The prenatal developmental profile of expression of opioid peptides and receptors in the mouse brain

Although the postnatal development of opioid systems of mammalian brain has been well studied, little is known about the ontogeny of and relationship between embryonic (E) opioid peptides and their receptors. Moreover, a simultaneous assessment of levels of the 3 classes of opioid peptides and their putative receptors during embryonal development has not been made. To this end, the ontogeny of opioid peptides and receptors in mouse brain were examined during the period E11.5 to postnatal day 1 (P1). Met-enkephalin, dynorphin and β-endorphin immunoreactivity were detected before their putative opioid receptors. β-Endorphin can be discerned as early as E11.5, whereas μ binding was first observed at E12.5. Although dynorphin and Met-enkephalin were measurable at the same time as β-endorphin, κ-receptors were not detected until E14.5 and δ sites were not found at all prenatally. Differences in immunoreactivity levels of the 3 peptides occur with dynorphin being lower than Met-enkephalin and β-endorphin, consistent with a low B max for κ binding. Expression of the 3 opioid peptides as well as μ and κ opioid receptors rapidly increase in parallel from E14.5 to E18.5. Interestingly, levels of β-endorphin diminish by P1, the stage at which a sharp rise of μ receptors occurs. In a comparative study of the binding of β-endorphin 1–31, its truncated form (1–27) and their N-acetyl derivatives to E14.5 brain membranes, β-endorphin 1–31 exhibited the highest affinity.