Metabolism of a heptapeptide opioid by rat brain and cardiac tissue.
Met-enkephalin-Arg6-Phe7 (E7) is converted to Met-enkephalin by rat striatal membranes; in contrast, Leu-enkephalin (E5) is inactivated by cleavage at the Tyr-Gly (aminopeptidase) and Gly-Phe sites (metalloendopeptidase). Conversion of E7 is inhibited by MK-421, and inactivation of E5 is inhibited by bestatin and Thiorphan. Purified brain angiotensin converting enzyme (EC 3.4.15.1) also converts E7 but a purified metalloendopeptidase acts on both E5 and E7 at the Gly-Phe site. Cleavage of E7-amide by metalloendopeptidase leads to release of Phe-Met-Arg-Phe-amide, a cardioactive neuropeptide. Rat heart, a potential target organ, does not convert E7-amide to release the cardioactive peptide but cleaves the Met5-Arg6 bond to release Met-enkephalin by an enzyme sensitive to MK-421.
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats
D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; C027511:enkephalin-Met, Arg(6)-Phe(7)-