Muscarinic receptor activation of phosphatidylcholine hydrolysis. Relationship to phosphoinositide hydrolysis and diacylglycerol metabolism
- Univ. of California, San Diego, La Jolla (USA)
We examined the relationship between phosphatidylcholine (PC) hydrolysis, phosphoinositide hydrolysis, and diacylglycerol (DAG) formation in response to muscarinic acetylcholine receptor (mAChR) stimulation in 1321N1 astrocytoma cells. Carbachol increases the release of (3H)choline and (3H)phosphorylcholine ((3H)Pchol) from cells containing (3H)choline-labeled PC. The production of Pchol is rapid and transient, while choline production continues for at least 30 min. mAChR-stimulated release of Pchol is reduced in cells that have been depleted of intracellular Ca2+ stores by ionomycin pretreatment, whereas choline release is unaffected by this pretreatment. Phorbol 12-myristate 13-acetate (PMA) increases the release of choline, but not Pchol, from 1321N1 cells, and down-regulation of protein kinase C blocks the ability of carbachol to stimulate choline production. Taken together, these results suggest that Ca2+ mobilization is involved in mAChR-mediated hydrolysis of PC by a phospholipase C, whereas protein kinase C activation is required for mAChR-stimulated hydrolysis of PC by a phospholipase D. Both carbachol and PMA rapidly increase the formation of (3H)phosphatidic acid ((3H)PA) in cells containing (3H)myristate-labeled PC. (3H)Diacylglycerol ((3H)DAG) levels increase more slowly, suggesting that the predominant pathway for PC hydrolysis is via phospholipase D. When cells are labeled with (3H)myristate and (14C)arachidonate such that there is a much greater 3H/14C ratio in PC compared with the phosphoinositides, the 3H/14C ratio in DAG and PA increases with PMA treatment but decreases in response to carbachol.
- OSTI ID:
- 5404154
- Journal Information:
- Journal of Biological Chemistry; (USA), Journal Name: Journal of Biological Chemistry; (USA) Vol. 264:25; ISSN 0021-9258; ISSN JBCHA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells
Sphingosine and phorbol ester preferentially stimulate phosphatidylethanolamine hydrolysis
Related Subjects
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLCHOLINE
ALCOHOLS
ALKALINE EARTH METALS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
ARACHIDONIC ACID
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL EFFECTS
BIOSYNTHESIS
CALCIUM
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARCINOGENS
CHOLINE
DRUGS
ELEMENTS
ENZYME ACTIVITY
ENZYMES
ESTERS
GLYCEROL
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
MAN
MEMBRANE PROTEINS
METABOLISM
METALS
MONOCARBOXYLIC ACIDS
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PARASYMPATHOMIMETICS
PHORBOL ESTERS
PHOSPHOLIPIDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
PROTEINS
QUATERNARY COMPOUNDS
RECEPTORS
SYNTHESIS
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
TUMOR CELLS
VERTEBRATES