Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Basselin, Mireille; Chang, Lisa; Seemann, Ruth; Bell, Jane M.; Rapoport, Stanley I.

doi:10.1038/sj.npp.1300611

Cited by 37 publications

(27 citation statements)

References 117 publications

(152 reference statements)

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“…Moreover, a fraction of the AA that is released by PLA 2 activation will be rapidly reincorporated into phospholipid, whereas the remainder will be lost by conversion to eicosanoids or other products, or by b-oxidation (82,83). Unesterified AA in plasma rapidly replaces the amount lost, and this replacement is proportional to PLA 2 activation (84,85). In our experiments, BEL alone inhibited free AA, but increased free AA when COX was inhibited at the same time.…”

Section: Discussionmentioning

confidence: 71%

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Nievergelt

Marazzi

Schoop³

et al. 2011

The Journal of Immunology

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The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever. We have profiled ginger constituents for robust effects on proinflammatory signaling and cytokine expression in a validated assay using human whole blood. Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1β expression in monocytes/macrophages. Both the calcium-independent phospholipase A2 (iPLA2)-triggered maturation and the cytosolic phospholipase A2 (cPLA2)-dependent secretion of IL-1β from isolated human monocytes were inhibited. In a fluorescence-coupled PLA2 assay, most major ginger phenylpropanoids directly inhibited i/cPLA2 from U937 macrophages, but not hog pancreas secretory phospholipase A2. The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA2 and methyl arachidonyl fluorophosphonate for cPLA2, with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 μg/ml) and 10-shogaol (2 μM) potently inhibited the release of PGE2 and thromboxane B2 (>50%) and partially also leukotriene B4 in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA2 and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle. The inhibition of i/cPLA2, the resulting attenuation of IL-1β secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.

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Section: Discussionmentioning

confidence: 71%

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Nievergelt

Marazzi

Schoop³

et al. 2011

The Journal of Immunology

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“…These regions included visual cortex layers I, IV, and VI, lateral habenular nucleus, medial geniculate nucleus, and inferior colliculus, which belong to central auditory and visual pathways (Brodal, 1981). We reported this observation (Basselin et al, 2003(Basselin et al, , 2005b, and suggested that it may underlie lithium's ability in human subjects to increase the amplitudes of P1/N1 components of auditory-evoked responses and of 65-P95 and P95-N125 components of visual-evoked responses (Fenwick and Robertson, 1983;Hegerl et al, 1990;Ulrich et al, 1990). In 65/83 regions, NMDA increased k* significantly in the control diet but not in the LiCl-fed rats.…”

Section: Physiological Parametersmentioning

confidence: 81%

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Basselin

Chang

Bell

et al. 2005

Neuropsychopharmacol

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103

132

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It has been proposed that lithium is effective in bipolar disorder (BD) by inhibiting glutamatergic neurotransmission, particularly via N-methyl-D-aspartate receptors (NMDARs). To test this hypothesis and to see if the neurotransmission could involve the NMDARmediated activation of phospholipase A 2 (PLA 2 ), to release arachidonic acid (AA) from membrane phospholipid, we administered subconvulsant doses of NMDA to unanesthetized rats fed a chronic control or LiCl diet. We used quantitative autoradiography following the intravenous injection of radiolabeled AA to measure regional brain incorporation coefficients k* for AA, which reflect receptormediated activation of PLA 2 . In control diet rats, NMDA (25 and 50 mg/kg i.p.) compared with i.p. saline increased k* significantly in 49 and 67 regions, respectively, of the 83 brain regions examined. The regions affected were those with reported NMDARs, including the neocortex, hippocampus, caudate-putamen, thalamus, substantia nigra, and nucleus accumbens. The increases could be blocked by pretreatment with the specific noncompetitive NMDA antagonist MK-801 ((5R,10S)-( + )-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine hydrogen maleate) (0.3 mg/kg i.p.), as well by a 6-week LiCl diet sufficient to produce plasma and brain lithium concentrations known to be effective in BD. MK-801 alone reduced baseline values for k* in many brain regions. The results show that it is possible to image NMDA signaling via PLA 2 activation and AA release in vivo, and that chronic lithium blocks this signaling, consistent with its suggested mechanism of action in BD.

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“…As k* responses to arecoline and quinpirole represent PLA 2 activation coupled to M 1, 3,5 and D 2 -like receptors, respectively (Bayon et al, 1997;DeGeorge et al, 1991;Hayakawa et al, 2001;Nilsson et al, 1998;Rapoport, 2001;Vial and Piomelli, 1995), the arecoline and quinpirole data suggest that lithium affects M 1,3,5 and D 2 -like receptor-mediated activation of PLA 2 in opposite ways. In contrast, LiCl has a more complex effect on k* responses in rats to DOI, an agonist of 5-HT 2A/2C receptors that also can be coupled to PLA 2 (Basselin et al, 2005;Felder et al, 1990;Qu et al, 2003).…”

Section: Discussionmentioning

confidence: 94%

“…This may explain why lithium does not reduce k* responses to the muscarinic receptor agonist arecoline (it even increases them), nor to the 5-HT 2A/2C receptor agonist, DOI, in most brain regions (responses are blocked by lithium in visual and auditory areas in which baseline values of k* are elevated) (Basselin et al, 2005(Basselin et al, , 2003b.…”

Section: Discussionmentioning

confidence: 99%

Chronic Lithium Chloride Administration to Unanesthetized Rats Attenuates Brain Dopamine D2-Like Receptor-Initiated Signaling Via Arachidonic Acid

Basselin

Chang

Bell

et al. 2005

Neuropsychopharmacol

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We studied the effect of lithium chloride on dopaminergic neurotransmission via D 2 -like receptors coupled to phospholipase A 2 (PLA 2 ). In unanesthetized rats injected i.v. with radiolabeled arachidonic acid (AA, 20:4 n-6), regional PLA 2 activation was imaged by measuring regional incorporation coefficients k* of AA (brain radioactivity divided by integrated plasma radioactivity) using quantitative autoradiography, following administration of the D 2 -like receptor agonist, quinpirole. In rats fed a control diet, quinpirole at 1 mg/kg i.v. increased k* for AA significantly in 17 regions with high densities of D 2 -like receptors, of 61 regions examined. Increases in k* were found in the prefrontal cortex, frontal cortex, accumbens nucleus, caudate-putamen, substantia nigra, and ventral tegmental area. Quinpirole, 0.25 mg/kg i.v. enhanced k* significantly only in the caudate-putamen. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, neither 0.25 mg/kg nor 1 mg/kg quinpirole increased k* significantly in any region. Orofacial movements following quinpirole were modified but not abolished by LiCl feeding. The results suggest that downregulation by lithium of D 2 -like receptor signaling involving PLA 2 and AA may contribute to lithium's therapeutic efficacy in bipolar disorder.

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Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Cited by 37 publications

References 117 publications

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Chronic Lithium Chloride Administration to Unanesthetized Rats Attenuates Brain Dopamine D2-Like Receptor-Initiated Signaling Via Arachidonic Acid

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