Further characterization of the in vitro hydrolysis of [Leu]- and [Met]enkephalin in rat plasma: HPLC-ECD measurement of substrate and metabolite concentrations.
Hydrolysis of [Leu]- and [Met]enkephalin was determined in whole rat plasma in vitro by using HPLC-ECD to measure Tyr, Tyr-Gly and Tyr-Gly-Gly formation. Although [Leu]- and [Met]enkephalin did not differ in Tyr or Tyr-Gly accumulation, the amount of Tyr-Gly-Gly resulting from [Met]enkephalin hydrolysis was greater than that resulting from [Leu]enkephalin hydrolysis, and [Met]enkephalin's half-life in plasma was slightly shorter than that of [Leu]enkephalin. By comparing metabolite formation in the presence and absence of peptidase inhibitors with high selectivity for their respective enzymes, these studies demonstrated that aminopeptidase M and angiotensin converting enzyme are the major peptidases that hydrolyze enkephalins in rat plasma.
Shibanoki
S
S
Department of Pharmacology, Nihon University School of Medicine, Tokyo, Japan.
Weinberger
S B
SB
Ishikawa
K
K
Martinez
J L
JL
D000596:Amino Acids / Q000378:metabolism; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D018826:CD13 Antigens; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000097:blood*; D004744:Enkephalin, Methionine / Q000097:blood*; D006868:Hydrolysis / Q000187:drug effects; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D002216:Captopril; D010450:Endopeptidases; D000626:Aminopeptidases; D018826:CD13 Antigens; C020071:dipeptidyl carboxypeptidase; D007703:Peptidyl-Dipeptidase A