Evidence for a Selective Processing of Proenkephalin B into Different Opioid Peptide Forms in Particular Regions of Rat Brain and Pituitary

Abstract

The distribution of 5 major products of proenkephalin B [dynorphin1-17, dynorphin B, dynorphin1-8, .alpha.-neo-endorphin and .beta.-neo-endorphin] was studied in regions of rat brain and pituitary. The distribution pattern of immunoreactive (ir) dynorphin B (= rimorphin) was similar to that of ir dynorphin1,17 with the highest concentrations being present in the posterior pituitary and the hypothalamus. HPLC [high performance liquid chromatography] and gel filtration showed the tridecapeptide dynorphin B was the predominant immunoreactive species recognized by dynorphin B antibodies in all brain areas and in the posterior pituitary. Two putative common precursor forms of dynorphin B and dynorphin1-17 with apparent MW of 3,200 and 6,000 were detected in brain and the posterior pituitary. The 3,200 dalton species coeluted with dynorphin1-32 on HPLC. Anterior pituitary ir-dynorphin B and ir-dynorphin1-17 consisted exclusively of the 6,000 dalton species. Concentrations of dynorphin1-8 were several times higher than those of dynorphin1-17 in striatum, thalamus and midbrain while posterior pituitary, hypothalamus, pons/medulla and cortex contained roughly equal concentrations of these 2 opioid peptides. No dynorphin1-8 was detected in the anterior pituitary. Concentrations of .beta.-neo-endorphin were similar to those of .alpha.-neo-endorphin in the posterior pituitary. In all brain tissues .alpha.-neo-endorphin was the predominant peptide, with tissue levels in striatum and thalamus .apprx. 20 times higher than those of .beta.-neo-endorphin. Differential proteolytic processing of proenkephalin B occurs within different reigons of brain and pituitary. Evidence is provided that, in addition to the paired basic amino acids -Lys-Arg- as the typical cleavage site for peptide hormone precursors, other cleavage signals also seem to exist for the processing of proenkephalin B.