The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: Whole-cell and single-channel studies

John C. Lopshire, Grant D. Nicol

Research output: Contribution to journalArticle

244 Scopus citations

Abstract

Treatment with proinflammatory prostaglandin E2 (PGE2) produced a transient sensitization of whole-cell currents elicited by the vanilloid capsaicin. The intracellular signaling pathways that mediate the initiation of this PGE2-induced sensitization of the capsaicin-elicited current in rat sensory neurons are not well established. Treatment with either forskolin (100 nM to 10 μM) or membrane-permeant analogs of cAMP, 8-bromo-cAMP (8-Br- cAMP) and chlorphenylthio-cAMP (10 μM to 1 mM), transiently sensitized neuronal responses elicited by capsaicin in a manner analogous to that produced by PGE2. The duration of sensitization was lengthened with increasing concentrations of forskolin; however, higher concentrations of 8- Br-cAMP or chlorphenylthio-cAMP led to a shortening of sensitization. The inactive analog of forskolin, dideoxy-forskolin, had no effect on capsaicin responses. Inclusion of the inhibitor of protein kinase A in the recording pipette completely suppressed the sensitization produced by PGE2 or forskolin. In recordings from membrane patches in the cell-attached configuration, the bath application of capsaicin evoked single-channel currents in which the level of channel activity was concentration-dependent and had an EC50 of 1.4 μM. These single-channel currents evoked by capsaicin exhibited an apparent reversal potential of +4 mV and were blocked by the capsaicin antagonist capsazepine. Exposure of the sensory neuron to either PGE2 or forskolin produced a large and transient increase in the mean channel activity (NP(o)) elicited by capsaicin, although the unitary conductance remained unaltered. Taken together, these observations suggest that modulation of the capsaicin-gated channel by the cAMP-protein kinase A signaling pathway enhanced the gating of these channels and consequently resulted in the sensitization of the whole-cell currents.

Original languageEnglish (US)
Pages (from-to)6081-6092
Number of pages12
JournalJournal of Neuroscience
Volume18
Issue number16
StatePublished - Aug 15 1998

Keywords

  • CAMP
  • Capsaicin
  • Neuronal excitability
  • Prostaglandin E
  • Protein kinase A
  • Sensitization

ASJC Scopus subject areas

  • Neuroscience(all)

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