Interaction between NMDA glutamatergic and nitrergic enteric pathways during in vitro ischemia and reperfusion

Filpa, Viviana; Carpanese, Elisa; Marchet, Silvia; Prandoni, Valeria; Moro, Elisabetta; Lecchini, Sergio; Frigo, Gianmario; Giaroni, Cristina; Crema, Francesca

doi:10.1016/j.ejphar.2015.01.021

Cited by 23 publications

(14 citation statements)

References 43 publications

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“…Accordingly, in this study, a significant reduction of NANC on-relaxations was observed after in vivo I/R and was not influenced by 4-MU treatment. In all experimental groups, sensitivity of NANC relaxations to the non-selective nitric oxide inhibitor, L-NAME, suggests that NO represents a major component of the inhibitory response 5,55,56 . In small intestine segments obtained from 4-MU treated and untreated control animals, NANC on-relaxations were insensitive to the iNOS inhibitor, 1400 W, reflecting the low number of constitutively iNOS expressing myenteric neurons in both groups.…”

Section: Discussionmentioning

confidence: 90%

Involvement of hyaluronan in the adaptive changes of the rat small intestine neuromuscular function after ischemia/reperfusion injury

Bistoletti

Bosi

Caon

et al. 2020

Sci Rep

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Intestinal ischemia/reperfusion (I/R) injury has severe consequences on myenteric neurons, which can be irreversibly compromised resulting in slowing of transit and hindered food digestion. Myenteric neurons synthesize hyaluronan (HA) to form a well-structured perineuronal net, which undergoes derangement when myenteric ganglia homeostasis is perturbed, i.e. during inflammation. In this study we evaluated HA involvement in rat small intestine myenteric plexus after in vivo I/R injury induced by clamping a branch of the superior mesenteric artery for 60 min, followed by 24 h of reperfusion. In some experiments, 4-methylumbelliferone (4-MU, 25 mg/kg), a HA synthesis inhibitor, was intraperitoneally administered to normal (CTR), sham-operated (SH) and I/R animals for 24 h. In longitudinal muscle myenteric plexus (LMMP) whole-mount preparations, HA binding protein staining as well as HA levels were significantly higher in the I/R group, and were reduced after 4-MU treatment. HA synthase 1 and 2 (HAS1 and HAS2) labelled myenteric neurons and mRNA levels in LMMPs increased in the I/R group with respect to CTR, and were reduced by 4-MU. The efficiency of the gastrointestinal transit was significantly reduced in I/R and 4-MU-treated I/R groups with respect to CTR and SH groups. In the 4-MU-treated I/R group gastric emptying was reduced with respect to the CTR, SH and I/R groups. Carbachol (CCh) and electrical field (EFS, 0.1-40 Hz) stimulated contractions and EFS-induced (10 Hz) NANC relaxations were reduced in the I/R group with respect to both CTR and SH groups. After I/R, 4-MU treatment increased EFS contractions towards control values, but did not affect CCh-induced contractions. NANC on-relaxations after I/R were not influenced by 4-MU treatment. Main alterations in the neurochemical coding of both excitatory (tachykinergic) and inhibitory pathways (iNOS, VIPergic) were also observed after I/R, and were influenced by 4-MU administration. Overall, our data suggest that, after an intestinal I/R damage, changes of HA homeostasis in specific myenteric neuron populations may influence the efficiency of the gastrointestinal transit. We cannot exclude that modulation of HA synthesis in these conditions may ameliorate derangement of the enteric motor function preventing, at least in part, the development of dysmotility. The gut is one of the most sensitive organs to ischemia-reperfusion (I/R) injury, which may occur in multiple clinical conditions, such as sepsis, shock, trauma, surgery, and is associated with high morbidity and mortality 1 .

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Section: Discussionmentioning

confidence: 90%

Involvement of hyaluronan in the adaptive changes of the rat small intestine neuromuscular function after ischemia/reperfusion injury

Bistoletti

Bosi

Caon

et al. 2020

Sci Rep

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“…Exendin-4 (100 nM–5 μM, Tocris, Bristol, UK, Eng et al, 1992; Raufman et al, 1992; Acuna-Goycolea and van den Pol, 2004); NO-donor L-arginine (1 mM, Sigma, St. Louis, MO, USA, Makara et al, 2007; Lameu et al, 2012); GLP-1R antagonist Exendin-3(9–39) (1 μM, Tocris, Eng et al, 1992; Raufman et al, 1992; Acuna-Goycolea and van den Pol, 2004); NOS inhibitor L-NAME (100 μM; Sigma, Makara et al, 2007; Poglia et al, 2011); nNOS inhibitor NPLA (1 μM; Tocris, Chow et al, 2012; Filpa et al, 2015; Gong et al, 2015); CB1 inverse agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl- N -(1-piperidyl) pyrazole-3-carboxamide(AM251; 1 μM; Tocris, Farkas et al, 2010, 2013); G-protein inhibitor GDP-β-S (2 mM; Sigma, Meis et al, 2002; Ponzio and Hatton, 2005; McDermott and Schrader, 2011); NO-scavenger CPTIO (1 mM, Sigma, Makara et al, 2007; Mironov and Langohr, 2007); TRPV1 antagonist 2E-N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-(1,1-dimethylethyl)phenyl]-2-Propenamide (AMG9810; 10 μM; Sigma, Vriens et al, 2011; Liu and Zhuo, 2014; Jian et al, 2016); anandamide-degrading enzyme FAAH inhibitor PF3845 (N-3-Pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide hydrate; 5 μM; Sigma, Lee et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways

Farkas

Vastagh

Farkas

et al. 2016

Front. Cell. Neurosci.

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Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM–5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs) frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9–39) (1 μM). Intracellular application of the G-protein inhibitor GDP-β-S (2 mM) impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP-1 on GnRH neurons. Blockade of nitric-oxide (NO) synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 100 μM) or N5-[Imino(propylamino)methyl]-L-ornithine hydrochloride (NPLA; 1 μM) or intracellular scavenging of NO by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO; 1 mM) partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using cannabinoid receptor type-1 (CB1) inverse-agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl) pyrazole-3-carboxamide (AM251; 1 μM). Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the transient receptor potential vanilloid 1 (TRPV1)-antagonist 2E-N-(2, 3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-(1, 1-dimethylethyl)phenyl]-2-Propenamide (AMG9810; 10 μM) or the fatty acid amide hydrolase (FAAH)-inhibitor PF3845 (5 μM) impeded the GLP-1-triggered endocannabinoid pathway indicating an anandamide-TRPV1-sensitive control of 2-arachidonoylglycerol (2-AG) production. Furthermore, GLP-1 immunoreactive (IR) axons innervated GnRH neurons in the hypothalamus suggesting that GLP-1 of both peripheral and neuronal sources can modulate GnRH neurons. RT-qPCR study confirmed the expression of GLP-1R and neuronal NO synthase (nNOS) mRNAs in GnRH-GFP neurons. Immuno-electron microscopic analysis revealed the presence of nNOS protein in GnRH neurons. These results indicate that GLP-1 exerts direct facilitatory actions via GLP-1R on GnRH neurons and modulates NO and 2-AG retrograde signaling mechanisms that control the presynaptic excitatory GABAergic inputs to GnRH neurons.

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“…Liu Z et al found that myocardial ischemia results in increased Glu release using a microdialysis method [ 74 ]. Consistent with this, intestinal I/R can also lead to increased Glu overflow [ 75 ]. Glutamate may be the key molecule in cellular ischemia.…”

Section: The Underlying Mechanisms Of Remote Ischemic Postconditiomentioning

confidence: 63%

“…It has also been reported that there may be cross talk between NMDA receptors and nitrergic pathways in the myenteric plexus; I/R enhanced both Glu and NO spontaneous overflow from isolated ileal segments [ 75 ].…”

Section: The Underlying Mechanisms Of Remote Ischemic Postconditiomentioning

confidence: 99%

Cerebral Ischemic Postconditioning Plays a Neuroprotective Role through Regulation of Central and Peripheral Glutamate

You

Feng

Xin

et al. 2018

BioMed Research International

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Following cerebral ischemia/reperfusion (I/R) injury, a series of pathophysiological processes are stimulated in both the central nervous system (CNS) and the periphery, including, but not limited to, the peripheral immune and endocrine systems and underregulation of the neuroendocrine-immune network. Glutamate (Glu) is an important excitatory neurotransmitter in the CNS; its excitotoxicity following cerebral ischemia has been a focus of study for several decades. In addition, as a novel immunoregulator, Glu also regulates immune activity in both the CNS and periphery and may connect the CNS and periphery through regulation of the neuroendocrine-immune network. Ischemic postconditioning (IPostC) is powerful and activates various endogenous neuroprotective mechanisms following cerebral I/R, but only a few studies have focused on the mechanisms associated with Glu to date. Given that Glu plays an important and complex pathophysiological role, the understanding of Glu-related mechanisms of IPostC is an interesting area of research, which we review here.

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Interaction between NMDA glutamatergic and nitrergic enteric pathways during in vitro ischemia and reperfusion

Cited by 23 publications

References 43 publications

Involvement of hyaluronan in the adaptive changes of the rat small intestine neuromuscular function after ischemia/reperfusion injury

Involvement of hyaluronan in the adaptive changes of the rat small intestine neuromuscular function after ischemia/reperfusion injury

Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways

Cerebral Ischemic Postconditioning Plays a Neuroprotective Role through Regulation of Central and Peripheral Glutamate

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