Pharmacological analysis of alpha(2)-adrenoceptor subtypes mediating analgesic, anti-inflammatory and gastroprotective actions.
Our previous findings suggest that alpha(2)-adrenoceptor stimulants induce gastroprotective action, the effect is likely to be mediated by alpha(2B)-adrenoceptor subtype. Clonidine (0.094 micromol/kg p.o.) and rilmenidine (0.014 micromol/kg p.o.) in gastroprotective dose range, as well as ST-91 (2.2 micromol/kg p.o.), a clonidine analogue showing higher affinity to alpha(2B)-adrenoceptor subtype than to alpha(2A)-one, inhibited the carrageenan-induced hyperalgesia in Randall-Selitto test, the antinociceptive action was reversed by yohimbine (5 micromol/kg s.c.) and the alpha(2B)-adrenoceptor antagonist prazosin (0.24 micromol/kg i.p.). Similarly, clonidine and rilmenidine in the same dose range reduced the oedema formation induced by carrageenan, yohimbine and the alpha(2A)-adrenoceptor antagonist BRL-44408 (3 micromol/kg i.p.) inhibited the anti-inflammatory effect; however, prazosin failed to affect it. These results suggest that alpha(2B/C)-like adrenoceptor subtype may be involved in the antihyperalgesic action, but not in the antiphlogistic effect of alpha(2)-adrenoceptor stimulants. The later effect may be mediated by alpha(2A)-like adrenoceptor subtype.
Gyires
K
K
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. gyirkla@net.sote.hu
Zádori
Z S
ZS
Shujaa
N
N
Al-Khrasani
M
M
Pap
B
B
Mózes
M M
MM
Mátyus
P
P
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D003000:Clonidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D010080:Oxazoles / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D000077769:Rilmenidine; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D010080:Oxazoles; D018341:Receptors, Adrenergic, alpha-2; C011266:ST 91; D003000:Clonidine; D000077769:Rilmenidine