title: Interaction between NMDA glutamatergic and nitrergic enteric pathways during in vitro ischemia and reperfusion.
abstract: Nitric oxide (NO) and glutamate, via N-methyl-d-aspartate (NMDA) receptors, participate to changes in neuromuscular responses after ischemic/reperfusion (I/R) injury in the gut. In the present study we investigated the existence of a possible interplay between nitrergic and NMDA receptor pathways in the guinea pig ileum after in vitro I/R injury, resorting to functional and biomolecular approaches. In normal metabolic conditions NMDA concentration-dependently enhanced both glutamate (analyzed by high performance liquid chromatography with fluorimetric detection) and NO (spectrophotometrically quantified as NO2(-) and NO3(-)) spontaneous overflow from isolated ileal segments. Both effects were reduced by the NMDA antagonists, (-)-AP5 (10µM) and 5,7-diCl-kynurenic acid (10µM, 5,7-diCl-KYN). N(ω)-propyl-l-arginine (1µM, NPLA) and 1400W (10µM), respectively, nNOS and iNOS inhibitors, reduced NMDA-stimulated glutamate overflow. After in vitro I/R, glutamate overflow increased, and returned to control values in the presence of NPLA and 1400W. NO2(-) and NO3(-) levels transiently increased during I/R and were reduced by both (-)-AP5 and 5,7-diCl-KYN. In longitudinal muscle myenteric plexus preparations, iNOS mRNA and protein levels increased after in vitro I/R; both parameters were reduced to control values by (-)-AP5 and 5,7-diCl-KYN. Both antagonists were also able to reduce ischemia-induced enhancement of nNOS mRNA levels. Protein levels of GluN1, the ubiquitary subunit of NMDA receptors, increased after I/R and were reduced by both NPLA and 1400W. On the whole, this data suggests the existence of a cross-talk between NMDA receptor and nitrergic pathways in guinea pig ileum myenteric plexus, which may participate to neuronal rearrangements occurring during I/R.
authors: Department of Clinical and Experimental Medicine, University of Insubria, via H.Dunant 5, I-21100 Varese, Italy.
authors: Viviana
authors: V
authors: Filpa
authors: Department of Clinical and Experimental Medicine, University of Insubria, via H.Dunant 5, I-21100 Varese, Italy.
authors: Elisa
authors: E
authors: Carpanese
authors: Department of Clinical and Experimental Medicine, University of Insubria, via H.Dunant 5, I-21100 Varese, Italy.
authors: Silvia
authors: S
authors: Marchet
authors: Department of Clinical and Experimental Medicine, University of Insubria, via H.Dunant 5, I-21100 Varese, Italy.
authors: Valeria
authors: V
authors: Prandoni
authors: Department of Internal Medicine and Therapeutics, Section of Pharmacology, via Ferrata 9, I-27100 Pavia, Italy.
authors: Elisabetta
authors: E
authors: Moro
authors: Department of Clinical and Experimental Medicine, University of Insubria, via H.Dunant 5, I-21100 Varese, Italy.
authors: Sergio
authors: S
authors: Lecchini
authors: Department of Internal Medicine and Therapeutics, Section of Pharmacology, via Ferrata 9, I-27100 Pavia, Italy.
authors: Gianmario
authors: G
authors: Frigo
authors: Department of Clinical and Experimental Medicine, University of Insubria, via H.Dunant 5, I-21100 Varese, Italy.
authors: Cristina
authors: C
authors: Giaroni
authors: Department of Internal Medicine and Therapeutics, Section of Pharmacology, via Ferrata 9, I-27100 Pavia, Italy.
authors: Francesca
authors: F
authors: Crema
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016202:N-Methylaspartate / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II
keywords: Glutamate; Ischemia/reperfusion; Myenteric plexus; NMDA receptors; Nitric oxide (PubChem CID: 145068)