α1‐Adrenergic Receptor Mediates Arachidonic Acid Release in Spinal Cord Neurons Independent of Inositol Phospholipid Turnover

Kanterman, R Y; Felder, Christian C.; Brenneman, Douglas E.; Alice, L.; Fitzgerald, Sandra C.; Axelrod, Julius

doi:10.1111/j.1471-4159.1990.tb01952.x

Cited by 48 publications

(16 citation statements)

References 44 publications

(40 reference statements)

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“…The physiologic role of 5-HT-receptor-stimulated release of arachidonic acid and subsequent eicosanoid formation in the hippocampus is not clear. Several other neurotransmitters have been shown to stimulate arachidonic acid mobilization in neurons, including norepinephrine, histamine, bradykinin, and glutamate (2)(3)(4)(5)36). Arachidonic acid and one of its lipoxygenase metabolites 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid can inhibit ion conductances and cause presynaptic inhibition ofneurotransmitter release (37) presumably through inhibition of Ca2+/ calmodulin-dependent protein kinase II, a protein thought to be involved in neurotransmitter release (38).…”

Section: -Ht-stimulatedmentioning

confidence: 99%

“…It is not clear from these studies whether the release of arachidonic acid is independent of inositolphospholipid turnover and whether the response is neural or glial in origin. Recent studies demonstrated a-adrenergic receptor stimulation caused arachidonic acid release from spinal cord, hippocampal, and cortical neurons, but not from glia cells, grown in primary culture that was independent of inositolphospholipid turnover (5).…”

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confidence: 99%

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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.

Felder

Kanterman²,

Alice³

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

183

119

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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 orign 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 [3U1lysophosphatidylcholine from [3UHcholine-labeled cells with no increase in the release of [3HUcholine or phospho[3Ulcholine. These data suggest that 5-UT stimulated the release of arachidonic acid in hippocampal neurons through the activation of phospholipase A2, independent of the activation of phospholipase C.The excitable membranes of the central nervous system are enriched in 20-carbon unsaturated fatty acids, particularly arachidonic acid (1). Arachidonic acid serves as a precursor to a number of biologically active acid lipids, including prostaglandins, leukotrienes, and thromboxanes. Arachidonic acid and its eicosanoid metabolites are released after activation ofcertain neurotransmitter receptors and may play a role in neurotransmission. Recent studies have demonstrated (2-4) receptor-mediated release of eicosanoids in brain cells in primary culture. N-Methyl-D-aspartate stimulated the release of arachidonic acid, 11-HETE, and 12-HETE (where HETE is hydroxyeicosatetraenoic acid) in striatal cells (2) as well as arachidonic acid in cerebellar granule cells (3). Bradykinin stimulated arachidonic acid mobilization from dorsal root ganglion neurons (4). It is not clear from these studies whether the release of arachidonic acid is independent of inositolphospholipid turnover and whether the response is neural or glial in origin. Recent studies demonstrated a-adrenergic receptor stimulation caused arachidonic acid release from spinal cord, hippocampal, and cortical neurons, but not from glia cells, grown in primary culture that was independent of inositolphospholipid turnover (5).Central serotonin (5-HT) receptors are involved in sleep, depression, hallucinations, anxiety, sexual behavior, memory, appetite control, and thermoregulation (6). 5-HT receptors exist as several subtypes and transduce their signals by way of multiple intracellular messengers (7). Types 1A, 1B, and 1D 5-HT receptors (5-HT1A, 5-HT1B, and 5-HTlD) modulate adenylate cyclase activity and types 1C and 2 5-HT (5-HT1c and 5-HT2) receptors incr...

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Section: -Ht-stimulatedmentioning

confidence: 99%

mentioning

confidence: 99%

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.

Felder

Kanterman²,

Alice³

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

183

119

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“…Thus, neither activation of phospholipase C nor a direct opening of receptormediated or voltage-dependent Ca 2+ channels appears to be involved in the ability of Ang II to release PGs in STTG1 and WITG2 and Ang-(l-7) in all three cell lines. In FRTL5 thyroid cells, 38 MadinDarby canine kidney (MDCK) cells 39 and spinal cord neurons, 40 a,-adrenergic agonists stimulate both inositol phospholipid hydrolysis and arachidonic acid release. However, enhancement of PG metabolism is dependent on extracellular Ca 2+ and most likely occurs through a Ca 2+ -dependent activation of phospholipase A 2 .…”

Section: +mentioning

confidence: 99%

Human astrocytes contain two distinct angiotensin receptor subtypes.

et al. 1991

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The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and VVITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose-dependent release of prostaglandin E, and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(l-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5-trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(l-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(l-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides -angiotensin-(1-7) and angiotensin-(2-8). Furthermore, the data also suggest that preferential production of angiotensin-(1-7) and angiotensin-(2-8) may be one level of regulation whereby a particular signal transduction pathway [i.e., calcium mobilization by angiotensin-(2-8) or prostaglandin release by angiotensin-(l-7)] is selectively activated. {Hypertension 1991;18:32-39)

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“…Astrocytes are capable of converting AA into prostaglandins, leukotrienes and epoxygenase metabolites [22,27] and are also sensitive to feedback regulation by prostaglandins [28]. Notably, activation of many of the metabotropic receptors in astrocytes is associated with AA release and production of prostaglandins [29][30][31][32][33][34][35]. We have shown in astrocytes, which were activated by different stimuli, that AA is mainly released by the Ca 2+ -dependent PLA 2 (cPLA 2 ).…”

Section: Polyunsaturated Fatty Acids Astrocytes and Brain Functionsmentioning

confidence: 99%

Regulation of intracellular calcium levels by polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, in astrocytes: possible involvement of phospholipase A2

2005

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-Pathological conditions in the brain, such as ischemia, trauma and seizure are accompanied by increased levels of free n-6 and n-3 polyunsaturated fatty acids (PUFA), mainly arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA,. A neuroprotective role has been suggested for PUFA. For investigation of the potential molecular mechanisms involved in neuroprotection by PUFA, we studied the regulation of the concentration of intracellular Ca 2+ ([Ca 2+ ] i ) in rat brain astrocytes. We evaluated the presence of extracellular PUFA and the release of intracellular PUFA. Interestingly, only the constitutive brain PUFA AA and DHA, but not eicosapentaenoic acid (EPA) had prominent effects on intracellular Ca 2+ . AA and DHA suppressed [Ca 2+ ] i oscillation, inhibited store-operated Ca 2+ entry, and reduced the amplitudes of Ca 2+ responses evoked by agonists of G protein-coupled receptors. Moreover, prolonged exposure of astrocytes to AA and DHA brought the cells to a new steady state of a moderately elevated [Ca 2+ ] i level, where the cells became virtually insensitive to external stimuli. This new steady state can be considered as a mechanism of self-protection. It isolates disturbed parts of the brain, because AA and DHA reduce pathological overstimulation in the tissue surrounding the damaged area. In inflammation-related events, frequently AA and DHA exhibit opposite effects. However, in astrocytes AA and DHA exerted comparable effects on [Ca 2+ ] i . Extracellularly added AA and DHA, but not EPA, were also able to induce the release of [ 3 H]AA from prelabeled astrocytes. Therefore, we also suggest the involvement of phospholipase A 2 activation and lysophospholipid generation in the regulation of intracellular Ca 2+ in astrocytes.

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α1‐Adrenergic Receptor Mediates Arachidonic Acid Release in Spinal Cord Neurons Independent of Inositol Phospholipid Turnover

Cited by 48 publications

References 44 publications

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.

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.

Human astrocytes contain two distinct angiotensin receptor subtypes.

Regulation of intracellular calcium levels by polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, in astrocytes: possible involvement of phospholipase A2

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