Abstract
Met-enkephalin and related proenkephalin A-derived peptides circulate in plasma at picomolar concentration as free, native pentapeptide and at nanomolar concentration in cryptic forms. We have optimized conditions for measurement of immunoreactive Met-enkephalin in plasma and for generation by trypsin and carboxypeptidase B of much greater amounts of total peptidase-derivable Met-enkephalin in plasma of rats, dogs, and humans. Free Met-enkephalin (11 pM) is constituted by native pentapeptide and its sulfoxide. Characterization of plasma total Met-enkephalin derived by peptidic hydrolysis revealed a small amount (38 pM) of Met-enkephalin associated with peptides of molecular mass less than 30,000 D, and probably derived from proenkephalin A, but much larger amounts of Met-enkephalin associated with albumin (1.2 nM) and with a globulin-sized protein (2.8 nM). Thus, plasma protein precursors for peptidase-derivable Met-enkephalin differ structurally and chemically from proenkephalin A. Met-enkephalin generated from plasma by peptidic hydrolysis showed naloxone-reversible bioactivity comparable to synthetic Met-enkephalin. Prolonged exposure of adult, male rats to restraint stress produced biphasic plasma responses, with peaks occurring at 30 s and 30 min in both free native and total peptidase-derivable Met-enkephalin. Repeated daily exposure to this 30-min stress resulted in adaptive loss of responses of both forms to acute restraint. Initial plasma responses of Met-enkephalin paralleled those of epinephrine and norepinephrine, but subsequently showed divergence of response. In conclusion, Met-enkephalin circulates in several forms, some of which may be derived from proteins other than proenkephalin A, and plasma levels of both free native, and peptidase-derivable Met-enkephalin are modulated physiologically.
Document Type
Article
Publication Date
3-1990
Digital Object Identifier (DOI)
https://doi.org/10.1172/JCI114513
Funding Information
These studies were supported by the Veterans Administration and the University of Kentucky Tobacco and Health Research Institute.
Repository Citation
Pierzchala, K. and Van Loon, G. R., "Plasma Native and Peptidase-Derivable Met-Enkephalin Responses to Restraint Stress in Rats. Adaptation to Repeated Restraint" (1990). Internal Medicine Faculty Publications. 256.
https://uknowledge.uky.edu/internalmedicine_facpub/256
Notes/Citation Information
Published in The Journal of Clinical Investigation, v. 85, issue 3.
© 1990 The American Society for Clinical Investigation, Inc.
The copyright holder has granted the permission for posting the article here.