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

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

Research output: Contribution to journalArticlepeer-review

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 (10 μM) and 5,7-diCl-kynurenic acid (10 μM, 5,7-diCl-KYN). Nω-propyl-L-arginine (1 μM, NPLA) and 1400W (10 μM), 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.

Original languageEnglish
Pages (from-to)123-131
Number of pages9
JournalEuropean Journal of Pharmacology
Volume750
DOIs
Publication statusPublished - Mar 5 2015

Keywords

  • Glutamate
  • Ischemia/reperfusion
  • Myenteric plexus
  • NMDA receptors

ASJC Scopus subject areas

  • Pharmacology
  • Medicine(all)

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