Atrial muscle stretch is widely believed to be the main stimulus for ANF release. However, we demonstrate in this study that although stretch induces an immediate increase in ANF output, this release rapidly decays even though hormone stores are not significantly depleted. In the present work, this phenomenon was studied in an isolated rat atria preparation using double isotope labelling. The tissue was labelled with $\rm\sp C$-leucine for 3 h followed by a 1 h chase, and then with $\rm\sp3H$-leucine for 1 h. A final 1 h chase period was conducted with the tissue under basal (0.2 g load) or stretched (5 g load) conditions. During this final chase period, the $\rm\sp C$-ANF represented ""older", stored ANF and the $\rm\sp3H$-ANF the "newly synthesized" peptide. Following both the $\rm\sp C$- and $\rm\sp3H$-leucine pulses, immunoprecipitable (IP) 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 immunoreactive (ir) ANF release and a decrease in the medium $\rm\sp C$-ANF specific activity (S.A.). However, no change was observed in the medium $\rm\sp3H$-ANF S.A. but the tissue S.A. tended to decrease. It is concluded that, in the basal state, a portion of ANF is immediately and preferentially released upon synthesis, while the remainder is presumably taken up into tissue stores and released from them at a lower rate. The secretory response to stretch was demonstrated to consist of a rapid, short-lived burst of newly synthesized ANF, suggesting an increased translocation of newly synthesized hormone into a stretch-sensitive, rapidly depletable pool. Given the nature of this pool, additional factors yet to be characterized likely come into play to maintain chronically elevated circulating levels of ANF.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/6833 |
| Date | January 1993 |
| Creators | Mangat, Harman. |
| Contributors | de Bold, A. J., |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 123 p. |
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