1. Academic Validation
  2. The antiarrhythmic peptide rotigaptide (ZP123) increases connexin 43 protein expression in neonatal rat ventricular cardiomyocytes

The antiarrhythmic peptide rotigaptide (ZP123) increases connexin 43 protein expression in neonatal rat ventricular cardiomyocytes

  • Cell Commun Adhes. 2006 Jan-Apr;13(1-2):21-7. doi: 10.1080/15419060600631375.
Martin Stahlhut 1 Jørgen S Petersen James K Hennan M Teresa Ramirez
Affiliations

Affiliation

  • 1 Zealand Pharma, Glostrup, Denmark.
Abstract

Rotigaptide (formerly ZP123) is a novel antiarrhythmic peptide that prevents uncoupling of connexin 43 (Cx43)-mediated, gap junction communication during acute metabolic stress. Since rotigaptide's long-term effects on Cx43 are unknown, we studied its effect on Cx43 protein levels at 24 h in neonatal ventricular myocytes. As determined by Western blot analysis, rotigaptide produced a dose-dependent increase in Cx43 protein expression that reached a maximum level at 100 nM. Furthermore, 100 nM rotigaptide markedly increased Cx43 immunoreactivity and Cx43-positive gap junctions as observed in immunocytochemical studies. Cycloheximide, an inhibitor of protein synthesis, was used to investigate rotigaptide's mechanism of action. Cycloheximide (10 microg/ml) reduced Cx43 protein levels to 39% of vehicle (17 mM ethanol) whereas cotreatment of 10 microg/ml cycloheximide with 100 nM rotigaptide reduced Cx43 protein levels to 56% of vehicle. Our findings suggest that rotigaptide's effect on Cx43 expression is partly due to increased biosynthesis.

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