Invertebrate opioid precursors: evolutionary conservation and the significance of enzymatic processing

Abstract

Invertebrate tissues contain mammalian-like proenkephalin, prodynorphin, and proopiomelanocortin. Amino acid sequence determination of these opioid gene products reveals the presence of various opioid peptides exhibiting high sequence identity with their mammalian counterparts. These associated peptides are flanked by dibasic amino acid residues, indicating cleavage sites. Together with the presence of various processing enzymes, i.e., neutral endopeptidase 24.11 and angiotensin-converting enzymes, this suggests that opioid precursor processing is also similar to that described in mammals. It is noted that the levels and/or activity of invertebrate neutral endopeptidase 24.11 can be upregulated by signaling molecules shown to perform the same function in mammals, i.e., morphine. Critical to opioid precursor processing are immunocytes that contain the precursors and transport processing enzymes to sites of inflammation, in part, to cleave these peptide precursors, thus liberating immune-stimulating molecules. Furthermore, in response to lipopolysaccharides, Met-enkephalin levels peak immediately and hours after the exposure, revealing a release and induction process. It appears that the opioid precursors and their processing enzymes first evolved in "simple" animals and the have been maintained and embellished during the course of evolution guided by conformational matching.