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Acta Physiologica 2011; Volume 203, Supplement 688
The 62nd National Congress of the Italian Physiological Society
9/25/2011-9/27/2011
Sorrento, Italy
C-TERMINAL CHROMOGRANIN A-DERIVED SERPININ AND PYROGLUTAMINATED SERPININ AS NOVEL CARDIAC -ADRENERGIC AGONISTS
Abstract number: P114
TOTA1 B, GENTILE1 S, PASQUA1 T, KOSHIMIZU3 H, CAWLEY3 NX, CERRA1,2 MC, LOH3 YP, ANGELONE1 T
1Dept of Cell Biology and
2Dept of Pharmaco-Biology, Univ. of Calabria, Italy
3Section of Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA
Chromogranin A (CgA) cleavage in the C terminus generates three peptides: serpinin (Ala26Leu), pyroglutaminated (pGlu)-serpinin (pGlu23Leu) and serpinin-Arg-Arg-Gly (Ala29Gly) (Koshimizu et al., 2011). In (neuro)endocrine cells, serpinin up-regulates granule biogenesis via a cAMP-protein kinase A-Sp1 pathway, while pGlu23Leu inhibits cell death. Here, by HPLC and ELISA, we detected serpinin peptides (mainly Ala29Gly and pGlu23Leu and a small amount of serpinin) in the rat heart. Using the Langendorff technique, we found that serpinin and pGlu23Leu exert dose-dependent positive inotropism and lusitropism at 11-165 nM. pGlu23Leu -dependent cardiostimulation is more potent than that elicited by serpinin, since it starts from 1 nM. Ala29Gly unaffected myocardial performance. Both pGlu23Leu and serpinin act as b-adrenergic agonists via a b1-Adrenergic Receptor/Adenylate Cyclase/cAMP/PKA pathway, contrary to the b-blocking profile of other CgA-derived cardiosuppressive peptides (vasostatin-1 and catestatin). In cardiac extracts, pGlu23Leu increased intracellular cAMP levels and phosphorylation of Phospholamban at ser16, ERK1/2 and GSK-3b.
On the whole, the presence of serpinin and pGlu23Leu in the heart, and their b-adrenergic-like behavior suggest that, together with other CgA-derived cardioactive fragments (Vasostatin and catestatin), these peptides contribute to orchestrate the normal cardiac function and the response to sympatho-chromaffin stimulation.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 203, Supplement 688 :P114