Abstract |
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.
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Authors | S G Khasar, A K Ouseph, B Chou, T Ho, P G Green, J D Levine |
Journal | Neuroscience
(Neuroscience)
Vol. 64
Issue 4
Pg. 1161-5
(Feb 1995)
ISSN: 0306-4522 [Print] United States |
PMID | 7753383
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Receptors, Prostaglandin E
- Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide
- Alprostadil
- Dinoprostone
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Topics |
- Alprostadil
(pharmacology)
- Animals
- Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide
(pharmacology)
- Dinoprostone
(pharmacology)
- Dose-Response Relationship, Drug
- Hindlimb
- Hyperalgesia
- Male
- Rats
- Rats, Sprague-Dawley
- Receptors, Prostaglandin E
(classification, physiology)
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