Journalartikel

Jahr der Veröffentlichung: 2009

Seiten: 227-241

Zeitschrift: European Journal of Cell Biology

Bandnummer: 88

Heftnummer: 4

ISSN: 0171-9335

eISSN: 1618-1298

DOI Link: https://doi.org/10.1016/j.ejcb.2008.11.001

Verlag: Elsevier

Abstract: 
Calcitonin gene-related peptide (CGRP)-alpha is expressed in heart ventricles in sensory nerves and cardiomyocytes. It modifies inotropism and induces ischaemic preconditioning. This study investigates the effect of CGRP-alpha on the contractile responsiveness of isolated adult ventricular rat cardiomyocytes and the effect of chronic hypertension on this interaction. Cardiomyocytes were isolated and paced at 0.5-2.0 Hz. Cell shortening was recorded via a line camera with a reading frame of 500 Hz. CGRP-alpha exerted a dual effect on cardiomyocytes with a positive contractile effect at 10nM and a negative contractile effect at 10pM. CGRP-alpha(8-37), a calcitonin receptor-like receptor (CRLR) antagonist, attenuated the positive contractile effect. H89, a protein kinase A antagonist, converted the positive contractile effect into a negative contractile effect. The negative contractile effect was converted again back to a positive contractile effect in the presence Of L-nitro arginine. In cardiomyocytes isolated from spontaneously hypertensive rats (SHR) the mRNA expression of CRLR and the receptor-associated modifier protein (RAMP)-2 were lower. However, on the protein level CLRL was up-regulated, RAMP2 expression remained unchanged, and eNOS expression was down-regulated in these cells. These cells responded with a pure positive contractile response. In Langendorff preparations, CGRP-alpha slightly reduced the rate pressure product in hearts from normotensive rats but it caused an increase in hearts from SHR. In conclusion, it is shown that CGRP-a exerts dual effects on cardiomyocytes favouring the negative contractile effect at very low concentrations. This effect is compensated in chronic pressure-overloaded hearts and converted into a positive inotropism. (C) 2008 Elsevier GmbH. All rights reserved.

Harvard-Zitierstil: Schlier, A., Schreckenberg, R., Abdallah, Y., Krasteva, G., Piper, H., Pfeil, U., et al. (2009) CGRP-α responsiveness of adult rat ventricular cardiomyocytes from normotensive and spontaneously hypertensive rats, European Journal of Cell Biology, 88(4), pp. 227-241. https://doi.org/10.1016/j.ejcb.2008.11.001

APA-Zitierstil: Schlier, A., Schreckenberg, R., Abdallah, Y., Krasteva, G., Piper, H., Pfeil, U., Kummer, W., & Schlueter, K. (2009). CGRP-α responsiveness of adult rat ventricular cardiomyocytes from normotensive and spontaneously hypertensive rats. European Journal of Cell Biology. 88(4), 227-241. https://doi.org/10.1016/j.ejcb.2008.11.001