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Evidence for a Differential Postnatal Development of Proenkephalin B (=Prodynorphin)-Derived Opioid Peptides in the Rat Hypothalamus

Department of Neuropharmacology, Max-Planck-Institut fur Psychiatrie D-8033 Martinsried, West Germany

Address requests for reprints to: Dr. Bernd R. Seizinger, Department of Neuropharmacology, Max-Planck-Institut fur Psychiatrie, D-8033 Martinsried, West Germany. Address correspondence to Dr. Bernd R. Seizinger’s present address: Department of Neurology and Genetics, Unit 7, Massachusetts General Hospital, Boston, Massachusetts 02117.

Abstract

The concentrations of immunoreactive (ir-) peptides derived from the opioid peptide precursors proenkephalin A (Met-enkephalin), proenkephalin B [dynprphin (DYN)-(1–17), dynorphin-(1–8), dynorphin B, -neoendorphin (-NEO-E), β-NEO-E] and proopiomelanocortin [β-endorphin (β-END)], and of the neursecretory hormones vasopressin and oxytocin increased between approximately 10-fold and 50-fold from birth t o adulthood in the rat hypothalamus.

Gel filtration and HPLC analysis of proenkephalin B-derived opioid peptides revealed that in 3-day-old rats the predominant portion of ir-dynorphih-(1–l7) and a substantial part of ir-dynorphin B consisted of a high (6000) mol wt species, a common precursor peptide for DYN-(1–17) and DYN B. In adults rats, however, authentic DYN-(1–17) and DYN B were found to be the major ir-forms.

The mol wt patterns of ir-DYN-(1-8), ir--NEO-E and ir-β-NEO-E did not differ between 3-day-old and adult rats and reflected predominantly the respectiye authentic opioid peptides. Taking into consideration the developmental changes in the mol wt pattern of ir-DYN-(l-17), authentic DYN-(1-17) was 5 times lower in concentration than DYN-(l-8) in 3-day-old rats, whereas in adults these opioid peptides occurred in equimolar concentrations. These findings suggest that the posttransla-tional processing of the precursor proenkephalin B changes in the course of postnatal development.

Ir-β-END in the hypothalamus of newborn and adult rats consisted exclusively of β-END-sized peptides which were not (unlike those in the intermediate pituitary lobe) -N-acetylated. Thus, in the hypothalamus, the enzymatic processing of the opioid peptide precursor proopiomelanocortin to β-END seems to be fully active at birth, in contrast to that of proenkephalin B. (Endocrinology 115: 926–935, 1984)

Received February 22, 1984.