Aging, cardiac proenkephalin mRNA and enkephalin peptides in the Fisher 344 rat.
Cardiac proenkephalin (PENK) mRNA, methionine-enkephalin (ME) and leucine-enkephalin (LE) were determined from 2 days of age through senescence in Fisher 344 rats. Tissues were collected at 2 days, 2 weeks, 1, 2, 3, 7, 19, and either 22 or 27 months of age. Hearts were dissected, extracted and assayed for ME and LE by radioimmunoassay (RIA) or for PENK mRNA by Northern blot analysis with a cDNA probe. Relative left ventricular (LV) PENK mRNA was low in 2 day animals and increased slowly between 2 weeks and 3 months of age. LV PENK mRNA then rose five to six-fold between 3 and 27 months of age. LV ME measurements were high in neonatal animals, declined to a nadir during development and then rose again as the animals matured and advanced in age. The pattern for right ventricular (RV) ME was similar. Atrial ME, also high at 2 days, declined thereafter and remained low. LE measurements in LV, RV and the atria followed patterns similar to those described for ME. To evaluate for peptides contributed by cardiac nerves, 3, 7 and 22-month-old animals were acutely sympathectomized for 24 h with 6-hydroxydopamine. No decline in LV ME and LE was observed in the 6-hydroxydopamine treated animals. These data suggest several conclusions regarding myocardial enkephalinergic systems: (a) tissue enkephalin and PENK mRNA increase with advancing age, (b) tissue enkephalins may not strictly correlate with the relative abundance of PENK mRNA, and (c) most myocardial enkephalins are non-adrenergic in origin. The age-associated patterns in both PENK mRNA, ME and LE suggest that physiological, maturational or behavioral events between 3 and 7 months of age initiate the up-regulation and subsequent expansion of cardiac enkephalinergic systems.
Caffrey
J L
JL
Gerontology Research Center, Baltimore, MD 21224.
Boluyt
M O
MO
Younes
A
A
Barron
B A
BA
O'Neill
L
L
Crow
M T
MT
Lakatta
E G
EG
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004743:Enkephalin, Leucine / Q000096:biosynthesis* / Q000235:genetics; D004744:Enkephalin, Methionine / Q000096:biosynthesis* / Q000235:genetics; D004745:Enkephalins / Q000235:genetics*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D013563:Sympathectomy, Chemical
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine