Muscarinic receptor activation of phosphatidylcholine hydrolysis. Relationship to phosphoinositide hydrolysis and diacylglycerol metabolism

Journal Article · Tue Sep 05 00:00:00 EDT 1989 · Journal of Biological Chemistry; (USA)

OSTI ID:5404154

Martinson, E A; Goldstein, D; Brown, J H ^[1]

---

1. 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), Vol. 264:25; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
RECEPTORS
GLYCEROL
BIOSYNTHESIS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHOLIPIDS
METABOLISM
ARACHIDONIC ACID
CALCIUM
CARBON 14 COMPOUNDS
CHOLINE
ENZYME ACTIVITY
MAN
PHOSPHOTRANSFERASES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
ALCOHOLS
ALKALINE EARTH METALS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBOXYLIC ACIDS
CARCINOGENS
DRUGS
ELEMENTS
ENZYMES
ESTERS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
METALS
MONOCARBOXYLIC ACIDS
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PARASYMPATHOMIMETICS
PHOSPHORUS-GROUP TRANSFERASES
PRIMATES
PROTEINS
QUATERNARY COMPOUNDS
SYNTHESIS
TRANSFERASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques