OBESTATIN SIGNALLING IN EXCISED FROG HEART

The aim of this research is to study the obestatin signalling on in vitro heart preparations of Rana ridibunda frog using pharmacological tools dissolved in or added to 0.1% or 0.01% dimethyl sulfoxide (DMSO). The application of increasing amounts of obestatin in the concentration range 1–1000 nmol/l significantly decreased the force of contraction of excised frog hearts in the presence of 0.1% DMSO. Propranolol entirely inhibited the effect of obestatin in the presence of DMSO without affecting the amplitudes of the force of contraction. Pertussis toxin, PP2 and U0126 completely blocked the obestatininduced decrease of the force of frog heart contractions. In the presence of XE991, 10 mol/l obestatin had no effect on the maximal force of contraction of the same preparations. Obestatin decreased the force of contraction when applied together with an inhibitor of cAMP-dependent protein kinase (PKA). It is suggested that the negative inotropic effect of obestatin observed in the presence of 0.1% DMSO is due to neuronal KCNQ channels modulation followed by a �-adrenergic receptor-dependent and PKA-independent decrease of the contraction force. Our data reveal for the first time the participation of neuronal MAPK kinase in obestatin signalling in the heart.