Opioid Peptides in Human Plasma: Evidence for Multiple Forms*

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Abstract
Studies were designed to assess whether the enkephalin- containing peptides and proteins present in the chromaffin granules of the adrenal medulla and in other secretory tissues, such as the neurohypophysis, could be found circulating in human blood. We analyzed human plasma acid acetone extracts chromatographed on Sephadex G-75 in acetic acid and found evidence for the existence of opioid peptides of several different molecularweights and a large number of peptides and small proteins which generate opioid activity after tryptic digestion. These compounds are different from and present in much greater quantities than previously described opioid peptides in human plasma, and are separate from dynorphin-immunoreactive compounds, which we also report in the blood. Expressed in leucine-enkephalin equivalents on a radioreceptor assay, we found 63.2 ± 6.5 (n = 4; mean ± SEM) pmol/ml plasma. One active peak from the Sephadex G-75 chromatography of human plasma (apparent mol wt, ∼3000) was examined by reverse phase highpressure liquid chromatography, tryptic digestion, and Sephadex G-50 chromatography. The results were consistent with the notion that this opioid active peptide contains an enkephalin sequence at its N-terminal, followed by a basic residue. Mild stress (2 min of deepknee bends) produced a 2- fold elevation in overall circulating opioid activity. The possibility is considered that the large enkephalin-containing peptides may have an endocrinefunction, independent of a role as enkephalin precursors.