Z Gastroenterol 2004; 42 - 39
DOI: 10.1055/s-2004-826940

Role of central nitric oxide in gastroprotection

K Gyires 1, K Fülöp 1, Z Zádori 1
  • 1Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest

Introduction: Our previous findings showed that intracerebroventricular (icv.) or intracisternal (ic.) administration of opioids elicits gastric mucosal protection in different ulcer models. The site of action was supposed to be the dorsal vagal complex where both opioid mu and delta receptors are located.

Aim: To analyse which mechanism may mediate the centrally originated gastroprotective effect of opioids.

Methods: The mucosal lesion was induced by oral administration of ethanol. The degree of mucosal damage was determined 1 hour later macroscopically. The drugs were injected either icv. or ic. 10min before the ethanol challenge.

Results:

  • The gastroprotective effect of [D-Ala2, D-Leu5]-enkephalin (DADLE), deltorphin II, [D-Ala2, Phe 4, Gly 5-ol]-enkephalin (DAGO) and beta-endorphin was inhibited by the NMDA receptor antagonsit dizocilpine (30 nmol/rat icv.) and the AMPA receptor antagonist NBQX (30 nmol/rat icv.).

  • NMDA (5–10 pmol/rat icv.) and AMPA (10–100 pmol/rat icv.) induced gastric mucosal protection.

  • The gastroprotective effect of NMDA and beta-endorphin was abolished by icv. administration of nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine.

  • The gastroprotective effect was also inhibited by the selective inhibitor of NO-sensitive guanylyl cyclase, ODQ (30 nmol/rat icv.).

  • Icv. injection of a cell permeable cGMP analog 8-Br-cGMP (100–150 nmol/rat icv.) induced mucosal protection, however, in a less extent than that induced by either opioids or NMDA.

Conclusion: Central nitric oxide may be involved in mediation of the gastroprotective effect of opioid peptides and NMDA.

The work was supported by Grant OTKA 032607 and ETT 389/2003.