Ischemic preconditioning increases the bioavailability of cardiac enkephalins
| Autor: | Antoine Younes, Salvatore Pepe, Darice Yoshishige, Edward G. Lakatta, James L. Caffrey |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Enkephalin Physiology Enkephalin Methionine Myocardial Ischemia Radioimmunoassay Ischemia Neuropeptide Myocardial Reperfusion In Vitro Techniques Rats Sprague-Dawley Coronary Circulation Physiology (medical) Internal medicine Animals Medicine cardiovascular diseases Protein Precursors Opioid peptide Receptor business.industry Enkephalins medicine.disease Myocardial Contraction Rats Proenkephalin Endocrinology Ischemic Preconditioning Myocardial cardiovascular system Ischemic preconditioning Cardiology and Cardiovascular Medicine business Enkephalin Leucine |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 289:H1652-H1661 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.01110.2004 |
| Popis: | Growing evidence suggests that cardiac enkephalins and their receptors are involved in ischemic preconditioning (IPC). Because there is no evidence for vesicular storage of small bioactive enkephalins in the heart, studies were designed to test the hypothesis that ischemia depletes cardiac enkephalins and that IPC preserves the same enkephalins by accelerating their processing from the larger proenkephalin precursor (PEP) pool. The precursors and two bioactive representatives, Met-enkephalin (ME) and Met-enkephalin-Arg-Phe (MEAP), were separated by size-exclusion chromatography and quantified by radioimmunoassay. Isolated perfused rat hearts were prepared and exposed to global ischemia. After 30 min of global ischemia and 40 min of reflow, the PEP pool was reduced (from 17.99 ± 1.52 to 14.20 ± 2.38 pmol/g wet wt), MEAP increased by 53%, and ME declined by 68%. The sum of the two smaller peptides was unchanged (9.78 ± 0.83 vs. 9.33 ± 2.81). Thus the total enkephalin peptide content was not altered (27.77 ± 1.69 vs. 24.10 ± 4.75). Peptide distribution after ischemia and reflow was also unaltered by pretreatment with peptidase inhibitors. However, when the hearts were preconditioned, the PEP pool remained significantly lower and both of the bioactive peptides, MEAP and ME, were elevated (+49% and +86%, respectively). The decline in the PEP pool was prevented by peptidase inhibition and the rise in MEAP was exaggerated. In separate protocols, synthetic enkephalins (ME, MEAP, and Leu-enkephalin) were added to the coronary inflow before 30 min of global ischemia and throughout the subsequent reflow. The added enkephalins (10−8M) had no inotropic effect on baseline function but completely prevented the mechanical dysfunction observed in untreated controls during reflow. Thus IPC appears to increase available bioactive enkephalins (MEAP + ME) within the heart by enhancing synthesis of precursors and their subsequent processing from the PEP pool. |
| Databáze: | OpenAIRE |
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