H. Mangat et Aj. Debold, STRETCH-INDUCED ATRIAL-NATRIURETIC-FACTOR RELEASE UTILIZES A RAPIDLY DEPLETING POOL OF NEWLY SYNTHESIZED HORMONE, Endocrinology, 133(3), 1993, pp. 1398-1403
Atrial muscle stretch is widely believed to be the main stimulus for a
trial natriuretic factor (ANF) release. However, a few reports have sh
own that although stretch induces an immediate increase in ANF output,
this release rapidly decays even though hormone stores are not signif
icantly depleted. In the present work, this phenomenon was studied in
an isolated rat atria preparation using double isotope labeling. The t
issue was labeled with [C-14]leucine for 3 h followed by a 1-h chase,
and then with [H-3]leucine for 1 h. A final 1-h chase period was condu
cted with the tissue under basal (0.2-g load) or stretched (5-g load)
conditions. During this final chase period, the [C-14]ANF represented
older, stored ANF and the [H-3]ANF represented the newly synthesized p
eptide. After both the [C-14]- and [H-3]leucine pulses, immunoprecipit
able isotope incorporated into ANF appeared in the chase medium within
the first 10 min and stabilized to lower levels after 20 min of chase
. Stretch resulted in an immediate significant increase in immunoreact
ive ANF release and a decrease in the medium [C-14]ANF specific activi
ty (SA). However, no change was observed in the medium [H-3]ANF SA but
the tissue SA tended to decrease. It is concluded that a portion of A
NF is immediately and preferentially released upon synthesis, while th
e remainder is taken up into tissue stores and released from them at a
lower rate. The secretory response to stretch was demonstrated to con
sist of a rapid, short-lived burst of newly synthesized ANF, suggestin
g an increased translocation of newly synthesized hormone into a stret
ch-sensitive, rapidly depletable pool. Given the nature of this pool,
additional factors yet to be characterized likely come into play to ma
intain chronically elevated circulating levels of ANF.