Effects of propranolol on phosphatidate phosphohydrolase and mitogen-activated protein kinase activities in A7r5 vascular smooth muscle cells.
High doses of propranolol inhibit phosphatidate phosphohydrolase (PAP) activity in intact cells, thus blocking metabolism of phosphatidic acid (PA), product of the phospholipase D (PLD) reaction. Vasopressin and phorbol ester activate PLD and ERK (extracellular signal-regulated protein kinase) mitogen-activated protein kinases in A7r5, a rat vascular smooth muscle cell line. Propranolol increased PA levels in intact A7r5 cells and inhibited cytosolic PAP and membrane calcium-independent phospholipase A2 but did not activate PLD or enhance agonist-induced PA accumulation. Incubation of cells with 200 microM propranolol for 10-45 min markedly elevated PA but caused only partial activation of ERKs. Propranolol and other lipophilic amines caused a time- and dose-dependent detachment of cells from their substrate. These results confirm that elevation of PA is not a strong signal for ERK activation and emphasize that caution should be exercised in using propranolol as a PAP inhibitor in intact cells.
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston 29425-2251, USA. meierke@musc.edu
K E
KE
Meier
K C
KC
Gause
A E
AE
Wisehart-Johnson
A C
AC
Gore
E L
EL
Finley
L G
LG
Jones
C D
CD
Bradshaw
A F
AF
McNair
K M
KM
Ella
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D010712:Phosphatidic Acids; D014667:Vasopressins; D011433:Propranolol; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010711:Phosphatidate Phosphatase; D013755:Tetradecanoylphorbol Acetate