Mediation of serotonin hyperalgesia by the cAMP second messenger system.

Abstract

In this study we have evaluated the second messenger system that might couple 5-HT1A receptor activation to produce peripheral hyperalgesia. The intradermal injection of the serotonin (5-hydroxytryptamine; 5-HT) receptor agonist for the 1A receptor subset (5-HT1A), (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthaline hydrobromide (8-OH DPAT) produces a dose-dependent hyperalgesia which was attenuated by a cAMP kinase inhibitor (the R-isomer of cyclic adenosine-3'-5'-monophosphate), but prolonged by the inhibition of endogenous phosphodiesterase by rolipram, supporting a role for the cAMP second messenger system. The 5-HT1A receptor agonist, 8-OH-DPAT, and the adenyl cyclase activator, forskolin administered together, produced an additive hyperalgesia, suggesting that the 5-HT1A receptor in peripheral terminals of the primary afferent neurons is positively coupled to the cAMP second messenger system in producing hyperalgesia. The inability of pertussis toxin to inhibit 8-OH DPAT-induced hyperalgesia further supports this hypothesis. The coupling of the 5-HT1A receptor to the cAMP second messenger system appears to be through guanine regulatory proteins since guanosine 5'-O-(3-thiotriphosphate) and cholera toxin both markedly enhanced 8-OH DPAT hyperalgesia. In further support of the role of guanine nucleotide regulatory proteins, guanosine 5'-O-(2-thiodiphosphate), as well as activators of inhibitory guanine regulatory proteins (the mu-opioid agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, and the adenosine A1 agonist, N6-cyclopentyladenosine, significantly attenuated 8-OH DPAT hyperalgesia.

• Authors: Y O Taiwo, P H Heller, J D Levine
• Journal: Neuroscience (Neuroscience) Vol. 48 Issue 2 Pg. 479-83 ( 1992) ISSN: 0306-4522 [Print] United States
• PMID: 1318516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Analgesics
• Enkephalins
• Protein Kinase Inhibitors
• Pyrrolidines
• Pyrrolidinones
• Receptors, Serotonin
• Tetrahydronaphthalenes
• Colforsin
• Serotonin
• Guanosine 5'-O-(3-Thiotriphosphate)
• N(6)-cyclopentyladenosine
• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Enkephalin, D-Penicillamine (2,5)-
• Cyclic AMP
• Rolipram
• Adenosine

Topics

• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Adenosine (analogs & derivatives, pharmacology)
• Analgesics (pharmacology)
• Animals
• Colforsin (pharmacology)
• Cyclic AMP (analogs & derivatives, pharmacology, physiology)
• Dose-Response Relationship, Drug
• Enkephalin, D-Penicillamine (2,5)-
• Enkephalins (pharmacology)
• Guanosine 5'-O-(3-Thiotriphosphate) (pharmacology)
• Hyperalgesia (physiopathology)
• Isomerism
• Male
• Nociceptors (drug effects, physiology)
• Pain (physiopathology)
• Protein Kinase Inhibitors
• Pyrrolidines (pharmacology)
• Pyrrolidinones (pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, Serotonin (drug effects, physiology)
• Rolipram
• Second Messenger Systems
• Serotonin (pharmacology, physiology)
• Tetrahydronaphthalenes (pharmacology)