beta-escin and pimobendan

We compared the effects of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS, an activator of G-protein), phorbol 12,13-dibutylate (PDB, an activator of protein kinase C) and pimobendan (an inotropic agent with Ca2+-sensitizing action) on the Ca2+ sensitivity of the contractile proteins in beta-escin-skinned muscle preparations obtained from rabbit left ventricles and mesenteric arteries. After the skinning procedure, when GTPgammaS (100 microM) or PDB (1 microM) was added to the Ca2+ solutions, pCa50 were significantly increased in preparations obtained from vascular smooth muscle, but not from cardiac muscle, indicating that G-protein- and protein kinase C-mediated direct Ca2+ sensitization may occur only in smooth muscle, but not in cardiac muscle. In contrast, pimobendan (50 microM) increased the Ca2+ responsiveness only in cardiac muscle. Therefore, we conclude that, in addition to the common regulatory factors affecting Ca2+ sensitivity such as intracellular pH and phosphorylation by protein kinase A, there are other means of regulation of Ca2+ sensitivity working differently in cardiac and in vascular smooth muscles.

Topics: Actin Cytoskeleton; Animals; Calcium; Cardiotonic Agents; Drug Evaluation, Preclinical; Enzyme Activation; Escin; Guanosine 5'-O-(3-Thiotriphosphate); Heart Ventricles; Histological Techniques; Mesenteric Arteries; Muscle, Smooth, Vascular; Phorbol 12,13-Dibutyrate; Protein Kinase C; Pyridazines; Rabbits