Z Gastroenterol 2005; 43 - 168
DOI: 10.1055/s-2005-869815

Role of adrenergic system in centrally induced gastroprotection of opioids

Z Zádori 1, K Fülöp 1, M Fekete 2, D Székács 2, M Tihanyi 1, H Kalász 1, K Gyires 1
  • 1Semmelweis University, Dept. of Pharmacology and Pharmacotherapy
  • 2Institute of Experimental Medicine of the Hungarian Academy of Sciences

Background: Our previous experiments showed that vagotomy decreased the gastroprotective effect of intracerebroventricularly (icv.) administered opioid peptides, suggesting the essential role of the vagal nerve in these protective processes. However, the inhibition was not complete, indicating possible role of other mechanisms. Our present experimental series aimed to examine the potential role of the adrenergic system in opioid-induced gastroprotection.

Methods: After 24 hour starvation male Wistar rats were given acidified ethanol orally. Gastric lesions were evaluated 1 hour later. Opioids were given icv. 10 minutes before the administration of ethanol. Propranolol was given either intraperitoneally (ip.) or icv. 20 and 10 minutes, respectively, before the injection of opioids. 6-hidroxydopamine (6-OHDA) was given icv. and ip. 6 and 3 days, respectively, before the challenge. The content of dopamine (DA) and noradrenaline (NA) of the NTS was measured by HPLC.

Results: 1. Propranolol both peripherally (6,76µmol/kg ip.) and centrally (34 nmol/rat icv.) significantly decreased the gastroprotective effect of icv. administered DAGO (0.009 nmol/rat), deltorphin II. (0.567 nmol/rat) and DPDPE (9.16 nmol/rat). 2. Sotalol intraperitoneally (10mg/kg) also attenuated the protective effect of icv. administered DAGO. 3. 6-OHDA given centrally (600 nmol/rat icv.) highly reduced the gastroprotective effect of icv. administered DAGO, deltorphin II and β-endorphin (0,01 nmol/rat). 4. 6-OHDA pretreatment peripherally (100mg/kg ip.) also markedly reduced the effect of DAGO. 5. Pretreatment with 6-OHDA (icv.) resulted in reduction of both the DA content (107,2 pg/mg tissue vs. 91,2 pg/mg tissue) and the NA content (1881,9 pg/mg tissue vs. 1439,8 pg/mg tissue) of the NTS.

Conclusions: Both central and peripheral adrenergic systems are likely to play a role in mediating the opioid-induced gastroprotection. However, further experiments are needed to elucidate whether the slight reduction of content of NA and DA after 6-OHDA treatment in the NTS may explain the dramatic decrease of the gastroprotective effect of opioid peptides.

The work was supported by grant ETT 389/2003.