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Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons
BACKGROUND: Triptans, 5-HT(1B/ID )agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1434723/ https://www.ncbi.nlm.nih.gov/pubmed/16549032 http://dx.doi.org/10.1186/1744-8069-2-10 |
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author | Morikawa, Tomoko Matsuzawa, Yoshiyasu Makita, Koshi Katayama, Yoshifumi |
author_facet | Morikawa, Tomoko Matsuzawa, Yoshiyasu Makita, Koshi Katayama, Yoshifumi |
author_sort | Morikawa, Tomoko |
collection | PubMed |
description | BACKGROUND: Triptans, 5-HT(1B/ID )agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca(2+ )channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca(2+ )channels are not yet documented. RESULTS: In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca(2+ )channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba(2+ )currents (I(Ba)) passing through Ca(2+ )channels. Zolmitriptan (0.1–100 μM) reduced the size of I(Ba )in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT(1B/1D )antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca(2+ )channel blockers inhibited the inhibitory action of zolmitriptan on I(Ba), compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT(1B/1D )receptor linked to G(i/o )pathway. CONCLUSION: It is concluded that this zolmitriptan inhibition of HVA Ca(2+ )channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan. |
format | Text |
id | pubmed-1434723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-14347232006-04-08 Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons Morikawa, Tomoko Matsuzawa, Yoshiyasu Makita, Koshi Katayama, Yoshifumi Mol Pain Research BACKGROUND: Triptans, 5-HT(1B/ID )agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca(2+ )channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca(2+ )channels are not yet documented. RESULTS: In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca(2+ )channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba(2+ )currents (I(Ba)) passing through Ca(2+ )channels. Zolmitriptan (0.1–100 μM) reduced the size of I(Ba )in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT(1B/1D )antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca(2+ )channel blockers inhibited the inhibitory action of zolmitriptan on I(Ba), compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT(1B/1D )receptor linked to G(i/o )pathway. CONCLUSION: It is concluded that this zolmitriptan inhibition of HVA Ca(2+ )channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan. BioMed Central 2006-03-20 /pmc/articles/PMC1434723/ /pubmed/16549032 http://dx.doi.org/10.1186/1744-8069-2-10 Text en Copyright © 2006 Morikawa et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Morikawa, Tomoko Matsuzawa, Yoshiyasu Makita, Koshi Katayama, Yoshifumi Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons |
title | Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons |
title_full | Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons |
title_fullStr | Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons |
title_full_unstemmed | Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons |
title_short | Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons |
title_sort | antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1434723/ https://www.ncbi.nlm.nih.gov/pubmed/16549032 http://dx.doi.org/10.1186/1744-8069-2-10 |
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