Differential regulation of evoked peptide release by voltage-sensitive calcium channels in rat sensory neurons

• Published in: Brain research 1996-03, Vol.712 (2), p.265-273
• Main Authors: Evans, Angela R., Nicol, Grant D., Vasko, Michael R.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bradykinin; Bradykinin - pharmacology; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Calcium Channels - metabolism; Calcium Channels - physiology; Capsaicin; Cells, Cultured; Dinoprostone - pharmacology; Electrophysiology; Fundamental and applied biological sciences. Psychology; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Isolated neuron and nerve. Neuroglia; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Neurons, Afferent - physiology; Neuropeptides - metabolism; Nifedipine; Nifedipine - pharmacology; omega-Conotoxin GVIA; Patch-Clamp Techniques; Peptides - pharmacology; Potassium - pharmacology; Prostaglandin; Rats; Rats, Sprague-Dawley; Release; Vertebrates: nervous system and sense organs; Voltage-sensitive calcium channel; w-Agatoxin; ω-Conotoxin
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)01447-0

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 PGE,-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 co-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 PGE 2 potentiated bradykinin- and capsaicin-evoked peptide release by 2–3-fold. Neither nifedipine nor ω-conotoxin GVIA attenuated the PGE 2-mediated potentiation of bradykinin-evoked release, and neither ω-conotoxin GVIA nor w-agatoxin IVA blocked the potentiation of capsaicin-evoked release induced by PGE 2. These results indicate that the sensitizing actions of PGE 2 as measured by enhanced peptide release, are not mediated by L-, N-, or P-type VSCC.