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 ac id (PA), product of the phospholipase D (PLD) reaction. Vasopressin an d phorbol ester activate PLD and ERK (extracellular signal-regulated p rotein kinase) mitogen-activated protein kinases in A7r5, a rat vascul ar smooth muscle cell line. Propranolol increased PA levels in intact A7r5 cells and inhibited cytosolic PAP and membrane calcium-independen t phospholipase A(2) but did not activate PLD or enhance agonist-induc ed PA accumulation. Incubation of cells with 200 mu M propranolol for 10-45 min markedly elevated PA but caused only partial activation of E RKs. Propranolol and other lipophilic amines caused a time- and dose-d ependent detachment of cells from their substrate. These results confi rm that elevation of PA is not a strong signal for ERK activation and emphasize that caution should be exercised in using propranolol as a P AP inhibitor in intact cells. (C) 1998 Elsevier Science Inc.