title: Alpha 1-adrenergic receptor-mediated increase in the mass of phosphatidic acid and 1,2-diacylglycerol in ischemic rat heart.
abstract: OBJECTIVE
  1,2-Diacylglycerol (1,2-DAG) and phosphatidic acid (PA) are produced by phospholipase C and D activity and play a key role as second messengers in receptor-mediated signal transduction. So far, little is known about alterations of endogenous 1,2-DAG and PA production during myocardial ischemia.
  
  
  METHODS
  Rat isolated perfused hearts were subjected to global ischemia, total lipids were extracted, and separated by thin-layer chromatography. The mass of PA and 1,2-DAG were quantified using laserdensitometric analysis of visualized lipids.
  
  
  RESULTS
  Compared to normoxic control values (1,2-DAG 713 +/- 45 ng/mg protein, PA 171 +/- 11 ng/mg protein), the myocardial content of 1,2-DAG and PA was unaltered after 10 min of ischemia. Prolonged myocardial ischemia (20 min), however, which was accompanied by marked overflow of endogenous norepinephrine, significantly increased the mass of both second messengers (1,2-DAG 1062 +/- 100 ng/mg protein, PA 340 +/- 29 ng/mg protein). The increase in PA and 1,2-DAG in response to ischemia was abolished by inhibition of ischemia-induced norepinephrine release as well as by alpha1-adrenergic blockade but unaffected by beta-adrenergic blockade. While inhibition of diacylglycerol kinase did not affect ischemia-induced increase in PA and 1,2-DAG, inhibition of phosphatidylinositol-specific phospholipase C activity significantly suppressed ischemia-induced increase in 1,2-DAG but did not affect endogenous production of PA indicating phospholipase C-independent formation of PA and activation of both, phospholipase C and D, in the ischemic heart.
  
  
  CONCLUSIONS
  Ischemia elicits an alpha1-adrenergic receptor-mediated increase in the mass of myocardial PA and 1,2-DAG. The increase in endogenous PA is suggested to be due to the activation of myocardial phospholipase D, whereas 1,2-DAG is formed predominantly by activation of phospholipase C in the ischemic heart.
authors.affiliation: Medizinische Klinik II, Medizinische Universität zu Lübeck, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kurz
authors.forename: I
authors.initials: I
authors.lastname: Schneider
authors.forename: R
authors.initials: R
authors.lastname: Tölg
authors.forename: G
authors.initials: G
authors.lastname: Richardt
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002855:Chromatography, Thin Layer; D003891:Desipramine / Q000494:pharmacology; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors; D004075:Diglycerides / Q000032:analysis*; D004963:Estrenes / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009638:Norepinephrine / Q000032:analysis; D010477:Perfusion; D010712:Phosphatidic Acids / Q000032:analysis*; D010880:Piperidines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D052999:Quinazolinones; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: C011439:1,2-diacylglycerol; D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004075:Diglycerides; D004963:Estrenes; D010712:Phosphatidic Acids; D010880:Piperidines; D011760:Pyrrolidinones; D011799:Quinazolines; D052999:Quinazolinones; D011942:Receptors, Adrenergic, alpha; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C058544:R 59949; D011433:Propranolol; D019852:Diacylglycerol Kinase; D010738:Type C Phospholipases; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin