Obestatin as contractile mediator of excised frog heart

The aim of this study is to investigate the mechanism of positive inotropic effect of obestatin on in vitro heart preparations of Rana ridibunda frog. The application of increasing amounts of obestatin in the concentration range from 1 μmol/l to 1 μmol/l significantly enhances the force of contraction of excised and cannulated frog hearts. This effect was partially reduced in the presence of prazosin (3 μmol/l). Propranolol (30 μmol/l), pertussis toxin (2 ng/ml) and the specific inhibitor of cAMP-dependent protein kinase (PKA) Rp-adenosine 3′,5′-cyclic monophosphothioate triethylamine (30 μmol/l) completely blocked the obestatin-induced increase of the force of frog heart contractions. It is concluded that, via its receptor molecule, obestatin activates neuronal pertussis toxin sensitive G-protein(s) that further enhance the secretion of epinephrine from sympathetic neurons. This epinephrine activates mainly the myocardial β-adrenoreceptors and PKA downstream targets, and is responsible for the observed positive inotropic effect of obestatin. An alternative explanation of our data is that obestatin directly enhances the effect of myocardial β-adrenergic signaling.