Journal article
Effects of Propranolol on Phosphatidate Phosphohydrolase and Mitogen-Activated Protein Kinase Activities in A7r5 Vascular Smooth Muscle Cells
Cellular signalling, Vol.10(6), pp.415-426
1998
Handle:
https://hdl.handle.net/2376/107383
PMID: 9720764
Abstract
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 A
2 but did not activate PLD or enhance agonist-induced PA accumulation. Incubation of cells with 200 μM propranolol for 10–45 min markedly elevated PA but caused only partial acivation 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.
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Details
- Title
- Effects of Propranolol on Phosphatidate Phosphohydrolase and Mitogen-Activated Protein Kinase Activities in A7r5 Vascular Smooth Muscle Cells
- Creators
- Kathryn E Meier - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USAKatrina C Gause - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USAApril E Wisehart-Johnson - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USAAngela C.S Gore - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USAEric L Finley - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USALinda G Jones - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USACynthia D Bradshaw - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USAAnthony F McNair - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USAKrishna M Ella - Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2251, USA
- Publication Details
- Cellular signalling, Vol.10(6), pp.415-426
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- Elsevier Inc
- Identifiers
- 99900547284701842
- Language
- English
- Resource Type
- Journal article