Analysis of the role of central and peripheral alpha2-adrenoceptor subtypes in gastric mucosal defense in the rat.
The present study confirmed our previous assumption on the crucial role of central alpha2B-like adrenoceptor subtype in gastric mucosal defense. It was found that beside clonidine, rilmenidine, an alpha2/imidazoline receptor agonist and ST-91, an alpha2B-adrenoceptor preferring agonist inhibited the mucosal lesions induced by ethanol given intracerebroventricularly (i.c.v.). The ED50 values for clonidine, rilmenidine and ST-91 are 0.2, 0.01 and 16 nmol/rat i.c.v., respectively. The effect was reversed by the intracerebroventricularly injected alpha2B/2C-adrenoceptor antagonists prazosin and ARC-239, indicating the potential involvement of central alpha2B/2C-adrenoceptor subtype in the protective action. The gastroprotective effect of adrenoceptor stimulants was reversed by bilateral cervical vagotomy, suggesting that vagal nerve is likely to convey the central action to the periphery. In gastric mucosa both nitric oxide and prostaglandins may mediate the centrally-induced effect, since both indomethacin and N(G)-nitro-L-arginine reversed the protective effect of alpha2-adrenergic stimulants. Though expression of mRNA of alpha2B-, as well as alpha2A- and alpha2C-adrenoceptor subtypes was demonstrated in gastric mucosa of the rat, the hydrophilic ST-91, given peripherally (orally, subcutaneously), failed to exert mucosal protection, in contrast with clonidine and rilmenidine which were also effective. Consequently, while peripheral alpha2B-adrenoceptors are not likely to be involved in gastric mucosal protection, activation of central alpha2B-like adrenoceptor subtype may initiate a chain of events, which result in a vagal dependent gastroprotective action.
Gyires
Klára
K
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary. gyirkla@pharma.sote.hu
Zádori
Zoltán S
ZS
Shujaa
Nashwan
N
Minorics
Renáta
R
Falkay
György
G
Mátyus
Péter
P
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000633:toxicity; D004247:DNA / Q000235:genetics; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000502:physiology*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D017933:Peripheral Nervous System / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology; D014628:Vagotomy
C547770:Adra2a protein, rat; C547773:Adra2b protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D000431:Ethanol; D004247:DNA