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 obestatin-induced decrease of the force of frog heart contractions. In the presence of XE991, 10 pmol/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 /3-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.
- Tyrosine kinase
ASJC Scopus subject areas