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1 Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224-6825; 2 Institut Universitaire de Technologie, Université d'Auvergne, 63172 Aubière Cedex, France; 3 Baker Medical Research Institute, Melbourne, Victoria 8008, Australia; and 4 Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, Texas 76107
Although preproenkephalin mRNA is
abundant in the heart, the myocardial synthesis and processing of
proenkephalin is largely undefined. Isolated working rat hearts were
perfused to determine the rate of myocardial proenkephalin synthesis,
its processing into enkephalin-containing peptides, their subsequent
release into the coronary arteries, and the influence of prior
sympathectomy. Enkephalin-containing peptides were separated by gel
filtration and quantified with antisera for specific COOH-terminal
sequences. Proenkephalin, peptide B, and
[Met5]enkephalin-Arg6-Phe7 (MEAP)
comprised 95% of the extracted myocardial enkephalins (35 pmol/g).
Newly synthesized enkephalins, estimated during a 1-h perfusion with
[14C]phenylalanine (4 pmol · h
1 · g wet wt1),
were rapidly cleared from the heart during a second isotope-free hour.
Despite a steady release of enkephalins into the coronary effluent (4 pmol · h1 · g wet wt1),
enkephalin replacement apparently exceeded its release, and tissue
enkephalins actually accumulated during hour 2. In contrast to the tissue, methionine-enkephalin accounted for more than half of
the released enkephalin. Chemical sympathectomy produced an increase in
total enkephalin content similar to that observed after 2-h control
perfusion. This observation suggested that the normal turnover of
myocardial enkephalin may depend in part on continued sympathetic influences.
enkephalin-containing peptides; opioids; rat heart
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