Alpha-2 adrenergic and opioid receptor-mediated gastroprotection.
Clonidine inhibited the development of gastric mucosal lesions induced by either acidified ethanol or indomethacin. The ED50 values were: 7.1 and 5.2 microg x kg(-1) orally, respectively. The gastroprotective effect was antagonised by the pre-synaptic alpha-2 antagonist yohimbine, the more selective alpha-2 antagonist Ch-38083 and the pre-synaptic alpha-2B antagonist prazosin. Moreover, the non-selective opioid receptor antagonist naloxone, the delta receptor selective naltrindole also reversed the clonidine-induced mucosal protective action. Clonidine was also effective following intracerebroventricular administration with the ED50 of 37 ng/rat against ethanol-induced mucosal damage. Our results suggest that: 1) the gastroprotective effect of clonidine is likely to be mediated by alpha-2B adrenoceptor subtype; 2) there is an interaction between pre-synaptic alpha-2 adrenoceptors and opioid system; and 3) clonidine can induce gastroprotection by central mechanism.
Gyires
K
K
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Müllner
K
K
Fürst
S
S
Rónai
A Z
AZ
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D003000:Clonidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D009292:Narcotic Antagonists; D018341:Receptors, Adrenergic, alpha-2; D011957:Receptors, Opioid; D000431:Ethanol; D003000:Clonidine; D007213:Indomethacin