Breakdown of small enkephalin derivatives and adrenal peptide E by human plasma

To provide information concerning the fate of opioid peptides introduced into the circulation of man, we have investigated the breakdown of the following peptides when incubated in human plasma: [Met]enkephalin, [Met]enkephalyl-Arg6-Phe7, [Met]enkephalyl-Arg6-Gly7-Leu8, [Met]enkephalyl-Arg6-Arg7-Val8-NH2 and the complex opioid, peptide E. We used a radioimmunoassay recognizing the amino-terminus of opioid peptides (assay for total opioid peptide-like immunoreactivity). The three small enkephalin derivatives were broken down considerably faster than the enkephalins themselves. The rate of loss of immunoreactivity was considerably reduced by bacitracin. When peptide E was incubated in human plasma, a relatively sustained level of opioid peptide-like immunoreactivity was seen. This was shown to be due, not only to the relatively slow aminopeptidase attack of the larger peptide, but also to the generation during breakdown of peptide E of [Leu]enkephalin and [Met]-enkephalin.