PMID- 8170501
OWN - NLM
STAT- MEDLINE
DCOM- 19940527
LR  - 20190725
IS  - 0028-1298 (Print)
IS  - 0028-1298 (Linking)
VI  - 349
IP  - 2
DP  - 1994 Feb
TI  - Tumor necrosis factor alpha decreases inositol phosphate formation and 
      phosphatidylinositol-bisphosphate (PIP2) synthesis in rat cardiomyocytes.
PG  - 175-82
AB  - Treatment of neonatal rat cardiomyocytes for 72 h in the presence of tumor 
      necrosis factor alpha (TNF alpha) (10 U/ml) lead to a decrease in basal and alpha 
      1-adrenoceptor-induced formation of the calcium-mobilizing second messenger 
      inositol trisphosphate (IP3) and its metabolites, IP2 and IP1, by 35 and 26%, 
      respectively. The synthesis of phosphatidylinositol bisphosphate (PIP2), the 
      substrate of PI-specific phospholipase C, was decreased by 45% following the TNF 
      alpha (10 U/ml) exposure. Time courses of TNF alpha (10 U/ml)-induced alterations 
      in rat cardiomyocytes showed a parallel decline of basal inositol phosphate 
      formation and PIP2 synthesis suggesting that the decrease in inositol phosphate 
      formation was due to the reduction in PIP2 synthesis. As the TNF alpha-induced 
      decrease of PIP2 synthesis was associated with a decreased synthesis of the 
      phospholipid phosphatidylinositol (PI), the precursor of PIP2, by 33%, the 
      decreased availability of PIP2 is apparently, at least in part, the result of the 
      decreased synthesis of PI. As an apparent functional consequence of the decrease 
      in IP3 formation following the TNF alpha exposure, the alpha 
      1-adrenoceptor-mediated induction of arrhythmias by 100 mumol/l noradrenaline + 
      10 mumol/l timolol was abolished in TNF alpha-pretreated rat cardiomyocytes. To 
      investigate one of the possible mechanisms of the TNF alpha-induced decrease of 
      PIP2 formation, the effect of TNF alpha pretreatment on glycerol-3-phosphate 
      dehydrogenase (GDH), a key enzyme of lipogenesis, was studied: Exposure of the 
      rat cardiomyocytes for 72 h to TNF alpha induced a concentration-dependent 
      decrease in GDH activity by maximally 55%.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Reithmann, C
AU  - Reithmann C
AD  - Medizinische Klinik I, Klinikum Grosshadern, Universitat Munchen, Germany.
FAU - Werdan, K
AU  - Werdan K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Inositol Phosphates)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Receptors, Adrenergic, alpha-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.1.- (Glycerolphosphate Dehydrogenase)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytoplasm/drug effects/enzymology/metabolism
MH  - Glycerolphosphate Dehydrogenase/metabolism
MH  - Heart/drug effects
MH  - Inositol Phosphates/*biosynthesis
MH  - Myocardial Contraction/drug effects
MH  - Myocardium/enzymology/*metabolism
MH  - Norepinephrine/metabolism
MH  - Phosphatidylinositol 4,5-Diphosphate
MH  - Phosphatidylinositol Phosphates/*biosynthesis
MH  - Rats
MH  - Receptors, Adrenergic, alpha-1/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Type C Phospholipases/metabolism
EDAT- 1994/02/01 00:00
MHDA- 1994/02/01 00:01
CRDT- 1994/02/01 00:00
PHST- 1994/02/01 00:00 [pubmed]
PHST- 1994/02/01 00:01 [medline]
PHST- 1994/02/01 00:00 [entrez]
AID - 10.1007/BF00169834 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 1994 Feb;349(2):175-82. doi: 
      10.1007/BF00169834.