Plasma protein(s) yields met-enkephalin-related peptides in near-micromolar concentrations when treated with pepsin.
Treatment of animal and human plasmas with pepsin yielded large quantities of immunoreactive methionine5-enkephalin (i-met-ENK). The concentrations measured after pepsin treatment were 0.1-0.5 microM, about 1000 times the normal circulating level of i-met-ENK (0.03-0.3 nM). The reaction was shown to be time and pH dependent and to involve the action of pepsin on a protein(s) of about 65,000 mol wt. Pepsin-generated i-met-ENK from rat plasma gave three major peaks during reverse phase HPLC, one of which (approximately 25% of the total) coeluted with methionine5-enkephalin sulfoxide and also completed in a radioreceptor assay for opiate-related substances. In addition, this material produced met-ENK-like effects on vascular permeability in rat skin and inhibited electrically induced contractions of the isolated guinea pig ileum in a naloxone-sensitive manner. The plasma substrate(s) that yielded i-met-ENK was distinguished from adrenal proenkephalins, since partially purified plasma substrate(s) did not liberate i-met-ENK upon digestion with trypsin and carboxypeptidase B. Although it is possible that these peptides differ from met-ENK in amino acid sequence, the results presented here suggest that met-ENK-related substances might be formed physiologically by the action of a pepsin-related processing enzyme(s) on plasma substrate(s). Such a mechanism would be analogous to that used in the renin-angiotensin system.
D000328:Adult; D000818:Animals; D001681:Biological Assay; D001798:Blood Proteins / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004744:Enkephalin, Methionine / Q000097:blood*; D006168:Guinea Pigs; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D010434:Pepsin A / Q000494:pharmacology*; D011863:Radioimmunoassay; D011869:Radioligand Assay; D051381:Rats; D013552:Swine
D001798:Blood Proteins; D004744:Enkephalin, Methionine; D010434:Pepsin A