Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 6 ·1990-03-00 ·Pages 2187-91

Felder CC, Kanterman RY, Ma AL, Axelrod J

Abstract

Serotonin (5-HT) stimulated the release of arachidonic acid in hippocampal neurons cocultured with glial cells but not in glial cultures alone. Similar results were observed for the 5-HT-stimulated release of inositol phosphates. These results suggest a neural but not glial origin of both responses. Pharmacological studies suggested that release of arachidonic acid and inositol phosphates was mediated by a type 2 5-HT (5-HT2) receptor. 5-HT-stimulated release of arachidonic acid was also detected in cortical neurons, which contain high levels of 5-HT2 receptors, but not striatum, spinal cord, or cerebellar granule cells, which have very low levels or are devoid of 5-HT2 receptors. The phorbol ester phorbol 12-myristate 13-acetate augmented the 5-HT-stimulated release of arachidonic acid but inhibited the 5-HT-stimulated release of inositol phosphates. 5-HT-stimulated release of arachidonic acid, but not inositol phosphates, was dependent on extracellular calcium. 5-HT stimulated the release of [3H]lysophosphatidylcholine from [3H]choline-labeled cells with no increase in the release of [3H]choline or phospho[3H]choline. These data suggest that 5-HT stimulated the release of arachidonic acid in hippocampal neurons through the activation of phospholipase A2, independent of the activation of phospholipase C.

MeSH Terms

Animals Arachidonic Acids/metabolism Cells, Cultured Eicosanoids/isolation & purification,metabolism Embryo, Mammalian Hippocampus/drug effects,enzymology Inositol Phosphates/metabolism Kinetics Lysophosphatidylcholines/metabolism Mice Mice, Inbred C57BL Neuroglia/cytology Neurons/cytology,drug effects,enzymology Phosphatidylinositols/metabolism Phospholipases/metabolism Phospholipases A/metabolism Phospholipases A2 Receptors, Serotonin/physiology Serotonin/pharmacology

Chemicals

Arachidonic Acids Eicosanoids Inositol Phosphates Lysophosphatidylcholines Phosphatidylinositols Receptors, Serotonin Serotonin Phospholipases Phospholipases A Phospholipases A2

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Felder C C

Section on Pharmacology, National Institute of Mental Health, Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20892.

Kanterman R Y

Ma A L

Axelrod J

References (38)

38 references, click to expand

Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A2.
Proc Natl Acad Sci U S A. 1987 Sep;84(18):6374-8 PMID: 2888113
Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors.
J Pharmacol Exp Ther. 1987 Aug;242(2):552-7 PMID: 3039120
Activation of N-methyl-D-aspartate-sensitive glutamate receptors stimulates arachidonic acid release in primary cultures of cerebellar granule cells.
Neuropharmacology. 1988 Jul;27(7):765-9 PMID: 2843786
NMDA receptors activate the arachidonic acid cascade system in striatal neurons.
Nature. 1988 Nov 3;336(6194):68-70 PMID: 2847054
Stimulation of arachidonic acid release and inhibition of mitogenesis by cloned genes for muscarinic receptor subtypes stably expressed in A9 L cells.
Proc Natl Acad Sci U S A. 1988 Nov;85(22):8698-702 PMID: 2847172
Formation and action of 8-hydroxy-11,12-epoxy-5,9,14-icosatrienoic acid in Aplysia: a possible second messenger in neurons.
Proc Natl Acad Sci U S A. 1989 Mar;86(5):1721-5 PMID: 2493649
Bradykinin stimulates phosphoinositide hydrolysis and mobilization of arachidonic acid in dorsal root ganglion neurons.
J Neurochem. 1989 Jul;53(1):95-101 PMID: 2542466
Potassium channels in cardiac cells activated by arachidonic acid and phospholipids.
Science. 1989 Jun 9;244(4909):1174-6 PMID: 2727703
Arachidonic acid and other fatty acids directly activate potassium channels in smooth muscle cells.
Science. 1989 Jun 9;244(4909):1176-9 PMID: 2471269
5-Hydroxytryptamine receptor "families".
FASEB J. 1989 Sep;3(11):2242-9 PMID: 2673898
Differentiation of 5-hydroxytryptamine2 receptor subtypes using 125I-R-(-)2,5-dimethoxy-4-iodo-phenylisopropylamine and 3H-ketanserin.
J Neurosci. 1989 Oct;9(10):3482-90 PMID: 2795135
G protein regulation of phospholipase A2.
Mol Neurobiol. 1989 Fall;3(3):155-71 PMID: 2510770
Intravenous injection of [1-14C]arachidonate to examine regional brain lipid metabolism in unanesthetized rats.
J Neurosci Res. 1989 Nov;24(3):413-23 PMID: 2512392
The selective loss of lysophospholipids in some commonly used lipid-extraction procedures.
Anal Biochem. 1974 Mar;58(1):238-45 PMID: 4825376
Effects of biogenic amines and psychotropic drugs on endogenous prostaglandin biosynthesis in the rat brain homogenates.
Biochem Pharmacol. 1978 Jan 15;27(2):213-8 PMID: 623677
Partial purification and properties of a rat brain phospholipase.
J Biol Chem. 1979 Oct 10;254(19):9761-5 PMID: 489566
Diglyceride lipase: a pathway for arachidonate release from human platelets.
Proc Natl Acad Sci U S A. 1979 Jul;76(7):3238-41 PMID: 290999
Serotonin receptor-mediated stimulation of bovine smooth muscle cell prostacyclin synthesis and its modulation by platelet-derived growth factor.
Proc Natl Acad Sci U S A. 1981 Nov;78(11):7134-8 PMID: 7031670
8-Hydroxy-2-(di-n-propylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonist.
J Med Chem. 1981 Aug;24(8):921-3 PMID: 6460101
[3H]Ketanserin (R 41 468), a selective 3H-ligand for serotonin2 receptor binding sites. Binding properties, brain distribution, and functional role.
Mol Pharmacol. 1982 Mar;21(2):301-14 PMID: 7099138
Eicosanoids: prostaglandins, thromboxanes, leukotrienes, and other derivatives of carbon-20 unsaturated fatty acids.
J Neurochem. 1982 Jan;38(1):1-14 PMID: 6286875
How is the level of free arachidonic acid controlled in mammalian cells?
Biochem J. 1982 Apr 15;204(1):3-16 PMID: 6810878
Relative activities of rat and dog platelet phospholipase A2 and diglyceride lipase. Selective inhibition of diglyceride lipase by RHC 80267.
J Biol Chem. 1982 Dec 10;257(23):14006-10 PMID: 7142192
Phospholipid and neutral lipid separation by one-dimensional thin-layer chromatography.
J Chromatogr. 1982 Oct 8;232(1):47-53 PMID: 7142338
Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands.
Biochem J. 1982 Sep 15;206(3):587-95 PMID: 7150264
8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site.
Eur J Pharmacol. 1983 May 20;90(1):151-3 PMID: 6223827
Rat hippocampal neurons in culture: responses to electrical and chemical stimuli.
J Neurophysiol. 1983 Dec;50(6):1249-64 PMID: 6663325
Separation of major prostaglandins, leukotrienes, and monoHETEs by high performance liquid chromatography.
J Immunol Methods. 1983 Nov 25;64(3):335-43 PMID: 6321597
5HT-receptor antagonist properties of SCH 23390 in vascular smooth muscle and brain.
Eur J Pharmacol. 1984 Oct 15;105(3-4):339-42 PMID: 6150862
Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse.
Proc Natl Acad Sci U S A. 1985 May;82(9):3035-9 PMID: 2859595
Identification of neutral active phospholipase C which hydrolyzes choline glycerophospholipids and plasmalogen selective phospholipase A2 in canine myocardium.
J Biol Chem. 1985 Jun 25;260(12):7295-303 PMID: 3997869
Receptor-binding properties in vitro and in vivo of ritanserin: A very potent and long acting serotonin-S2 antagonist.
Mol Pharmacol. 1985 Jun;27(6):600-11 PMID: 2860558
Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors.
Brain Res. 1985 Nov 4;346(2):231-49 PMID: 4052777
Intracellular Ca2+ mobilization by arachidonic acid. Comparison with myo-inositol 1,4,5-trisphosphate in isolated pancreatic islets.
J Biol Chem. 1986 Mar 15;261(8):3501-11 PMID: 3081507
Phospholipase A2 and phospholipase C are activated by distinct GTP-binding proteins in response to alpha 1-adrenergic stimulation in FRTL5 thyroid cells.
Proc Natl Acad Sci U S A. 1986 Oct;83(19):7201-5 PMID: 3020540
3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors.
Mol Pharmacol. 1987 Feb;31(2):194-9 PMID: 3543649
Lipoxygenase metabolites of arachidonic acid as second messengers for presynaptic inhibition of Aplysia sensory cells.
Nature. 1987 Jul 2-8;328(6125):38-43 PMID: 2439918
The molecular heterogeneity of protein kinase C and its implications for cellular regulation.
Nature. 1988 Aug 25;334(6184):661-5 PMID: 3045562

Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.87.6.2187

Published

1990-03-00

Pages

2187-91

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC53651

Subset

External Links

PubMed source DOI: 10.1073/pnas.87.6.2187 PMC Full Text View journal details

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Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis.

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