The effect of nitric oxide donors on nitric oxide synthase-expressing myenteric neurones in culture.
Neurogastroenterol Motil
; 18(4): 307-15, 2006 Apr.
Article
en En
| MEDLINE
| ID: mdl-16553586
ABSTRACT
Previously, we demonstrated that intestinal inflammation leads to a postinflammatory loss of nitric oxide synthase (NOS)-expressing myenteric neurones and motility disturbances. Here, we investigated whether high NO concentrations could be responsible for the decrease in NOS neurones. Myenteric neurone cultures, prepared from guinea-pig small intestine, were incubated with NO donors [sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1)]. After fixation, NOS neurones were identified by NADPH diaphorase staining and neurone-specific enolase (NSE)-positive neuronal content was assessed with an enzyme-linked immunosorbent assay (ELISA)-based method. Twenty-four hours incubation with SIN-1 (10(-3) mol L(-1)) or SNP (10(-4) mol L(-1) or higher) reduced the number of NADPH diaphorase-positive neurones. SNP incubation did not affect the NSE-positive neuronal content. Shorter incubations (SNP 4 and 12 h) had no significant effect. The SNP-induced reduction was reversed by glutathione (GSH), but not by NO- or O-scavengers, whereas GSH depletion enhanced the decrease. The NO-dependent guanylate cyclase-blocker 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) did not affect the SNP effect. This reduction can be explained by either specific apoptosis of NOS neurones or downregulation of NOS activity. However, TdT-mediated X-dUTP nick end labelling (TUNEL stainings argue in favour of the latter. In conclusion, the NO donor SNP decreases the number of NOS-expressing myenteric neurones time and concentration dependently, without affecting the amount of neuronal material. Glutathione plays an important protective role.
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Bases de datos:
MEDLINE
Asunto principal:
Óxido Nítrico Sintasa
/
Donantes de Óxido Nítrico
/
Plexo Mientérico
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Neurogastroenterol Motil
Asunto de la revista:
GASTROENTEROLOGIA
/
NEUROLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Bélgica