Is there more than one prostaglandin E receptor subtype mediating hyperalgesia in the rat hindpaw?
Five synthetic prostaglandin E analogs (11-deoxyPGE1, 17-phenyl-ol-trinor prostaglandin E2, enisoprost, MB28767 and misoprostol) have been evaluated for their ability to produce mechanical hyperalgesia in rats. The Randall-Selitto paw withdrawal model of mechanical hyperalgesia was used. Following intradermal injections (2.5 microliters) into the dorsal surface of the hindpaw, each prostaglandin E analog produced a dose-dependent (1-1000 ng) decrease in nociceptive threshold (i.e. hyperalgesia). Hyperalgesia produced by 17-phenyl-ol-trinor prostaglandin E2 and MB28767, was inhibited by the prostaglandin E1 antagonist SC19220 (7.5 ng), while the hyperalgesia produced by 11-deoxyprostaglandin E1, enisoprost and misoprostol was not inhibited by this antagonist. Hyperalgesia produced by all five analogs was significantly attenuated or completely blocked by inhibiting stimulatory guanine nucleotide-binding regulatory protein with guanosine 5'-O-(2-thiodiphosphate), adenylyl cyclase with 2'5'-dideoxyadenosine and protein kinase A with WIPTIDE. These results suggest the presence of more than one prostaglandin E-receptor subtype, which mediate hyperalgesia, predominantly via the cAMP second messenger system, in the hindpaw of the rat.
Khasar
S G
SG
Department of Medicine, University of California, San Francisco 94143, USA.
Ouseph
A K
AK
Chou
B
B
Ho
T
T
Green
P G
PG
Levine
J D
JD
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb; D006930:Hyperalgesia; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000145:classification* / Q000502:physiology
D018078:Receptors, Prostaglandin E; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D000527:Alprostadil; D015232:Dinoprostone