Involvement of phosphoinositide turnover in ouabain inotropism.
We examined whether ouabain activities phospholipases and reinforces contraction force of papillary muscles through resultant second messengers. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), the inhibitor of phospholipase C (PLC), abolished the ouabain inotropy in rabbit papillary muscles. Calphostin C, the specific inhibitor of protein kinase C (PKC), also depressed the ouabain inotropy. 12-O-Tetradecanoylphorbor-13-acetate (TPA), the specific activator of PKC, enhanced the beat-to-beat phasic contractility at low concentrations. Radioenzymatic assay revealed that ouabain treatment doubled diacylglycerol (DG) content in excised papillary muscles. We concluded that ouabain activates PLC, and the resultant second messenger, DG, augments the cardiac contraction force through activation of PKC.
Gotoh
H
H
Department of Physiology, Iwate Medical University School of Medicine, Japan.
Kamiyama
A
A
Shibayama
R
R
Sawada
M
M
Kashimoto
T
T
D000818:Animals; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009281:Naphthalenes; D010042:Ouabain / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D015290:Second Messenger Systems; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D009281:Naphthalenes; D010716:Phosphatidylinositols; D011083:Polycyclic Compounds; D010042:Ouabain; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate