Bradykinin Stimulates Arachidonic Acid Release Through the Sequential Actions of an <i>sn</i>‐1 Diacylglycerol Lipase and a Monoacylglycerol Lipase

Allen, Ann C.; Gammon, Charles M.; Ousley, Andrea; McCarthy, Ken D.; Morell, Pierre

doi:10.1111/j.1471-4159.1992.tb09372.x

Cited by 67 publications

(30 citation statements)

References 49 publications

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“…DAG has many functions in cells, and in addition to directly activating effector molecules, it can serve as a substrate for enzymes that generate alternative signalling lipids [2]. One such pathway involves the hydrolysis of DAG by a DAG lipase (DAGL) activity, the initial step in a pathway that was first studied in the context of arachidonic acid (AA) release in platelets and mast cells [3][4][5]. This involves the hydrolysis of DAG at the sn-1 position to generate 2-arachidonolyglycerol (2-AG) followed by a monoacylglycerol lipase (MAGL)-dependent hydrolysis of 2-AG to generate AA.…”

Section: The Diacylglycerol Lipases: Elusive Enzymes Responsible For mentioning

confidence: 99%

The diacylglycerol lipases: structure, regulation and roles in and beyond endocannabinoid signalling

Reisenberg

Singh

Williams

et al. 2012

Phil. Trans. R. Soc. B

127

121

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The diacylglycerol lipases (DAGLs) hydrolyse diacylglycerol to generate 2-arachidonoylglycerol (2-AG), the most abundant ligand for the CB 1 and CB 2 cannabinoid receptors in the body. DAGL-dependent endocannabinoid signalling regulates axonal growth and guidance during development, and is required for the generation and migration of new neurons in the adult brain. At developed synapses, 2-AG released from postsynaptic terminals acts back on presynaptic CB 1 receptors to inhibit the secretion of both excitatory and inhibitory neurotransmitters, with this DAGL-dependent synaptic plasticity operating throughout the nervous system. Importantly, the DAGLs have functions that do not involve cannabinoid receptors. For example, 2-AG is the precursor of arachidonic acid in a pathway that maintains the level of this essential lipid in the brain and other organs. This pathway also drives the cyclooxygenase-dependent generation of inflammatory prostaglandins in the brain, which has recently been implicated in the degeneration of dopaminergic neurons in Parkinson's disease. Remarkably, we still know very little about the mechanisms that regulate DAGL activity-however, key insights can be gleaned by homology modelling against other a/b hydrolases and from a detailed examination of published proteomic studies and other databases. These identify a regulatory loop with a highly conserved signature motif, as well as phosphorylation and palmitoylation as post-translational mechanisms likely to regulate function.

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Section: The Diacylglycerol Lipases: Elusive Enzymes Responsible For mentioning

confidence: 99%

The diacylglycerol lipases: structure, regulation and roles in and beyond endocannabinoid signalling

Reisenberg

Singh

Williams

et al. 2012

Phil. Trans. R. Soc. B

127

121

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“…These findings may reflect a phospholipase A 2 -independent pathway for arachidonic acid release in the peripheral terminals of afferent neurons. Such a pathway is present in afferent neuron cell bodies, where bradykinin-induced arachidonic release occurred predominantly by the sequential actions of an sn-1 diacylglycerol lipase and a monoacylglycerol lipase, rather than by a phospholipase A 2 -mediated hydrolysis of phospholipids (Allen et al, 1992). The diacylglycerol lipase inhibitor RHC 80267 did have an apparent inhibitory effect in four of the six fibers studied; however, in two fibers, no effect was noted, and overall, there was not a significant difference in the average number of action potentials evoked by bradykinin.…”

mentioning

confidence: 99%

“…Bradykinin B 2 receptor stimulation evokes the release of arachidonic acid in afferent neurons (Burgess et al, 1989;Gammon et al, 1989;Allen et al, 1992) and depolarizes the membrane potential of vagal (Undem and Weinreich, 1993;Kajekar et al, 1999) and dorsal root ganglion (Burgess et al, 1989;McGuirk and Dolphin, 1992) neuron cell bodies. In addition, bradykinin inhibits a calcium-dependent potassium current responsible for an afterspike hyperpolarization in nodose ganglion neurons (Weinreich et al, 1995).…”

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confidence: 99%

“…The binding of bradykinin to B 2 receptors in afferent neurons stimulates a variety of intracellular events (Bevan, 1996), including the mobilization of arachidonic acid (Burgess et al, 1989;Gammon et al, 1989;Allen et al, 1992). We have previously found that guinea pig airway C-fiber responses to bradykinin were not inhibited by indomethacin (Kajekar et al, 1999), indicating that cyclooxygenase products are not primarily responsible for the excitatory action of bradykinin, although they play a role in bradykinin-induced sensitization of afferent neurons in other tissues (Dray et al, 1992;Weinreich et al, 1995;Maubach and Grundy, 1999).…”

mentioning

confidence: 99%

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A Role for TRPV1 in Bradykinin-Induced Excitation of Vagal Airway Afferent Nerve Terminals

Carr¹,

Kollárik²,

Meeker³

et al. 2002

J Pharmacol Exp Ther

116

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Using single-unit extracellular recording techniques, we have examined the role of the vanilloid receptor-1 (VR1 aka TRPV1) in bradykinin-induced activation of vagal afferent C-fiber receptive fields in guinea pig isolated airways. Of 17 airway C-fibers tested, 14 responded to bradykinin and capsaicin, 2 fibers responded to neither capsaicin nor bradykinin, and 1 fiber responded to capsaicin but not bradykinin. Thus, every bradykinin-responsive C-fiber was also responsive to capsaicin. Bradykinin (200 l of 0.3 M solution) evoked a burst of approximately 130 action potentials in C-fibers. In the presence of the TRPV1 antagonist capsazepine (10 M), bradykinin evoked 83 Ϯ 9% (n ϭ 6; P Ͻ 0.01) fewer action potentials. Similarly, the TRPV1 blocker, ruthenium red (10 M), inhibited the number of bradykinin-evoked action potentials by 75 Ϯ 10% (n ϭ 4; P Ͻ 0.05). In the presence of 5,8,11,14-eicosatetraynoic acid (10 M), an inhibitor of lipoxygenase and cyclooxygenase enzymes, the number of bradykinin-induced action potentials was reduced by 76 Ϯ 10% (n ϭ 6; P Ͻ 0.05). Similarly, a combination of the 12-lipoxygenase inhibitor, baicalein (10 M) and the 5-lipoxygenase inhibitor ZD2138 [6-[3-fluoro-5-[4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl])phenoxy-methyl]-1-methyl-2-quinolone] (10 M) caused significant inhibition of bradykinin-induced responses. Our data suggest a role for lipoxygenase products in bradykinin B 2 receptor-induced activation of TRPV1 in the peripheral terminals of afferent C-fibers within guinea pig trachea.The pharmacological activation of primary afferent neurons often involves the opening of ligand-gated ion channels such as 5-hydroxytryptamine 3 receptors, P2X purinoceptors, nicotinic acetylcholine receptors, and vanilloid receptor 1 (TRPV1), the first cloned capsaicin receptor (Wood and Docherty, 1997). Upon agonist binding to these channels, their ion pore opens, allowing the influx of cations, resulting in a membrane depolarization of sufficient magnitude to initiate action potentials. Bradykinin, an endogenous metabolite of the kallikrein-kinin system often associated with inflammation, also directly activates nociceptive-like afferent neurons, but does so via metabotropic G protein-coupled bradykinin B 2

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“…Phospholipase D (PLD) and phosphatidate phosphohydrolase (PAP) or phospholipase C (PLC) can liberate DAG from host phospholipid membranes. DAG can then be converted to AA by the diacylglycerol (DAGL) and monoacylglycerol (MAGL) lipases (19) (Fig. 1).…”

mentioning

confidence: 99%

Francisella tularensis LVS Induction of Prostaglandin Biosynthesis by Infected Macrophages Requires Specific Host Phospholipases and Lipid Phosphatases

et al. 2014

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Francisella tularensis induces the synthesis of prostaglandin E 2 (PGE 2 ) by infected macrophages to alter host immune responses, thus providing a survival advantage to the bacterium. We previously demonstrated that PGE 2 synthesis by F. tularensis-infected macrophages requires cytosolic phospholipase A2 (cPLA 2 ), cyclooxygenase 2 (COX-2), and microsomal prostaglandin E synthase 1 (mPGES1). During inducible PGE 2 synthesis, cPLA 2 hydrolyzes arachidonic acid (AA) from cellular phospholipids to be converted to PGE 2 . However, in F. tularensis-infected macrophages we observed a temporal disconnect between Ser505-cPLA 2 phosphorylation (a marker of activation) and PGE 2 synthesis. These results suggested to us that cPLA 2 is not responsible for the liberation of AA to be converted into PGE 2 by F. tularensis-infected macrophages. Utilizing small-molecule inhibitors, we demonstrated that phospholipase D and diacylglycerol lipase were required for providing AA for PGE 2 biosynthesis. cPLA 2 , on the other hand, was required for macrophage cytokine responses to F. tularensis. We also demonstrated for the first time that lipin-1 and PAP2a contribute to macrophage inflammation in response to F. tularensis. Our results identify both an alternative pathway for inducible PGE 2 synthesis and a role for lipid-modifying enzymes in the regulation of macrophage inflammatory function.

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Bradykinin Stimulates Arachidonic Acid Release Through the Sequential Actions of an sn‐1 Diacylglycerol Lipase and a Monoacylglycerol Lipase

Cited by 67 publications

References 49 publications

The diacylglycerol lipases: structure, regulation and roles in and beyond endocannabinoid signalling

The diacylglycerol lipases: structure, regulation and roles in and beyond endocannabinoid signalling

A Role for TRPV1 in Bradykinin-Induced Excitation of Vagal Airway Afferent Nerve Terminals

Francisella tularensis LVS Induction of Prostaglandin Biosynthesis by Infected Macrophages Requires Specific Host Phospholipases and Lipid Phosphatases

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