title: Additive inhibitory effects of calcitonin and capsaicin on voltage activated calcium channel currents in nociceptive neurones of rat.
abstract: Calcitonin, a peptide hormone expressed in C-cells of the thyreoid gland, as well as capsaicin, isolated from chili, both, modify intracellular signalling in nociceptive neurones. The pathways triggered by the activation of either of these receptors results in a modulation of the intracellular calcium ([Ca(2+)](i)) concentration. While the regulation of [Ca(2+)](i) depends on many factors, voltage activated calcium channels (VACCs) are a major gate for the calcium entry into neurones. Here we describe the changes of voltage gated calcium channel currents (I(Ca(V))) induced by calcitonin and/or capsaicin. Currents were recorded using adequate solutions and voltage protocols with the whole cell patch-clamp technique. When the channels were opened by a depolarisation to 0 mV, both substances reduce the peak I(Ca(V)) (calcitonin (10nM): 29.3 ± 3.9%; capsaicin (0.5 μM): 41.1 ± 7.7%). While the effect of calcitonin was voltage dependent, capsaicin shifted the largest current to the more hyperpolarizing range (peak current from -10 to -20 mV). A subsequent co-application of either of the two substances (with a pre-application of either 3 min or 60 min) results in an additive reduction of the currents, and prevents the capsaicin-induced shift of the current-voltage relation. Therefore, we hypothesize, that the activation of either of the two receptors reduces I(Ca(V)) by different cellular binding sites of the channel protein triggering channel opening. These findings may be useful to understand cellular mechanisms of pain modulation and might help to find better treatments for neuropathic pain.
authors.affiliation: Universitätsklinikum Essen, Klinik für Neurologie, Hufelandstr. 55, 45122 Essen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hagenacker
authors.forename: D
authors.initials: D
authors.lastname: Ledwig
authors.forename: D
authors.initials: D
authors.lastname: Büsselberg
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D002116:Calcitonin; D002211:Capsaicin; D002118:Calcium