To determine whether the sensitizing actions of prostaglandins on sensory neurons are due to modulation of voltage-sensitive calcium channels (VSCC) we examined the effects of inhibiting these channels on PGE2-induced enhancement of evoked peptide release from isolated dorsal root ganglion neurons. The inhibitory effects of the VSCC blockers on stimulated release were dependent upon the type of chemical agent used to evoke the release. Bradykinin-stimulated release of immunoreactive substance P (iSP) and calcitonin gene-related peptide (iCGRP) was attenuated by the N-type VSCC blocker, ω-conotoxin GVIA (100 nM), but was unaffected by blockade of L-type (1 μM nifedipine) or P-type (200 nM ω-agatoxin IVA) VSCC. In contrast, potassium-stimulated release of peptides was inhibited by nifedipine, but not by ω-conotoxin GVIA or ω-agatoxin IVA. None of the VSCC blockers tested attenuated capsaicin-stimulated release of iSP and iCGRP. The combination of 1 μM nifedipine and 100 nM ω-conotoxin GVIA reduced the whole cell calcium current 89% ± 1.7%. Administration of 100 nM PGE2 potentiated bradykinin- and capsaicin-evoked peptide release by 2-3-fold. Neither nifedipine nor ω-conotoxin GVIA attenuated the PGE2-mediated potentiation of bradykinin-evoked release, and neither ω-conotoxin GVIA nor ω-agatoxin IVA blocked the potentiation of capsaicin-evoked release induced by PGE2. These results indicate that the sensitizing actions of PGE2 as measured by enhanced peptide release, are not mediated by L-, N-, or P-type VSCC.
- voltage-sensitive calcium channel
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