Effects of norepinephrine and cardiotrophin-1 on phospholipase D activity and incorporation of myristic acid into phosphatidylcholine in rat heart.
The present study is part of a project on phospholipase D (PLD) in cardiac hypertrophy and analyzed effects on PLD activity of two growth stimuli, norepinephrine (NE) and cardiotrophin-1 (CT-1), in incubated rat heart. Phosphatidylcholine (PC) was labeled by (3)H-myristic acid. PLD produced (3)H-phosphatidylethanol ((3)H-PEth) from (3)H-PC in the presence of ethanol and maintained a basal formation of (3)H-PEth. Short-term and long-term exposure to NE for 2 or 13 h, respectively, enhanced the formation of (3)H-PEth, which was blocked by prazosin. Long-term pretreatment with NE or CT-1 increased the incorporation of (3)H-myristic acid into PC, which was blocked by atenolol. When the (3)H-PEth formation was expressed as a fraction of (3)H-PC, PLD activity seemingly was unchanged (NE) or markedly reduced (CT-1); the true effects, namely, stimulation by NE and nonresponsiveness towards CT-1, were unraveled by atenolol (NE) or when PLD activity was expressed as (3)H-PEth per ng protein. In conclusion, alpha-adrenoceptor activation increased PLD activity. Long-term treatment with NE (via beta-receptors) or CT-1 enhanced the (3)H-myristic acid incorporation into a PC compartment, that was not available for the alpha-receptor-mediated PLD activation. These results were discussed in regard to cellular mechanisms of cardiac hypertrophy and to the transphosphatidylation assay of PLD.
Department of Pharmacology, Johannes-Gutenberg-University of Mainz, Obere Zahlbacher Str. 67, D-55101 Mainz, Germany.
Tobias
T
Weismüller
Jochen
J
Klein
Konrad
K
Löffelholz
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D019814:Myristic Acid / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology; D010713:Phosphatidylcholines / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D016207:Cytokines; D010713:Phosphatidylcholines; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D019814:Myristic Acid; C092073:cardiotrophin 1; D010739:Phospholipase D; D009638:Norepinephrine