caa a22 4500 44537408X CHVBK 20180317142957.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00540-011-1168-6 doi (NATIONALLICENCE)springer-10.1007/s00540-011-1168-6 Dexmedetomidine and clonidine inhibit the function of NaV1.7 independent of α2-adrenoceptor in adrenal chromaffin cells [Elektronische Daten] [Toyoaki Maruta, Takayuki Nemoto, Shinya Satoh, Tasuku Kanai, Toshihiko Yanagita, Akihiko Wada, Isao Tsuneyoshi] Purpose: Besides being administered systemically for sedation and analgesia, α2-agonists such as dexmedetomidine and clonidine have been administered with intrathecal, epidural, or perineural injections, leading to an antinociceptive effect at the spinal cord or peripheral nerve level. However, the mechanism for this remains unclear. In the present study, we examined whether dexmedetomidine and clonidine could inhibit the function of tetrodotoxin-sensitive Na+ channels, which play important roles in the generation of pain. Methods: Cultured bovine adrenal chromaffin cells expressing the tetrodotoxin-sensitive Nav1.7 Na+ channel isoform were incubated in KRP buffer containing 2μCi 22NaCl for 5min without or with dexmedetomidine or clonidine in the absence or presence of veratridine, α-scorpion venom, β-scorpion venom, Ptychodiscus brevis toxin-3 or ouabain. Cells were then washed and counted radioactively. Results: Dexmedetomidine and clonidine reduced veratridine-induced 22Na+ influx via Nav1.7 in a concentration-dependent manner (EC50=50μM and 530μM), even in the presence of ouabain, an inhibitor of Na+, K+-ATPase. Dexmedetomidine and clonidine shifted the concentration-response curve of veratridine for 22Na+ influx downward without altering the EC50 of veratridine. Atipamezole and yohimbine, α2-antagonists, did not prevent the inhibition of veratridine-induced 22Na+ influx by dexmedetomidine. Dexmedetomidine and clonidine combined with lidocaine induced more inhibition of veratridine-induced 22Na+ influx than each drug did individually. Atipamezole and yohimbine did not prevent the lidocaine-enhancing effect of dexmedetomidine and clonidine. Conclusion: Dexmedetomidine and clonidine inhibit the function of Nav1.7 independent of α2-adrenoceptor. These results may lead to a deeper understanding of the peripheral antinociceptive effects of α 2-agonists. Japanese Society of Anesthesiologists, 2011 Adrenal chromaffin cell nationallicence Dexmedetomidine nationallicence Clonidine nationallicence Tetrodotoxin-sensitive Na+ channels nationallicence NaV1.7 nationallicence Maruta Toyoaki Department of Anesthesiology, Miyazaki Medical College, University of Miyazaki, 889-1692, Miyazaki, Japan aut Nemoto Takayuki Department of Pharmacology, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan aut Satoh Shinya Department of Otorhinolaryngology, Head and Neck Surgery, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan aut Kanai Tasuku Department of Pharmacology, School of Pharmaceutical Sciences Welfare, Kyusyu University of Health and Welfare, Miyazaki, Japan aut Yanagita Toshihiko Department of Pharmacology, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan aut Wada Akihiko Department of Sports Health and Welfare, Faculty of Social Welfare, Kyusyu University of Health and Welfare, Miyazaki, Japan aut Tsuneyoshi Isao Department of Anesthesiology, Miyazaki Medical College, University of Miyazaki, 889-1692, Miyazaki, Japan aut Journal of Anesthesia Springer Japan 25/4(2011-08-01), 549-557 0913-8668 25:4<549 2011 25 540 https://doi.org/10.1007/s00540-011-1168-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00540-011-1168-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Maruta Toyoaki Department of Anesthesiology, Miyazaki Medical College, University of Miyazaki, 889-1692, Miyazaki, Japan aut NATIONALLICENCE 700 1- Nemoto Takayuki Department of Pharmacology, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan aut NATIONALLICENCE 700 1- Satoh Shinya Department of Otorhinolaryngology, Head and Neck Surgery, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan aut NATIONALLICENCE 700 1- Kanai Tasuku Department of Pharmacology, School of Pharmaceutical Sciences Welfare, Kyusyu University of Health and Welfare, Miyazaki, Japan aut NATIONALLICENCE 700 1- Yanagita Toshihiko Department of Pharmacology, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan aut NATIONALLICENCE 700 1- Wada Akihiko Department of Sports Health and Welfare, Faculty of Social Welfare, Kyusyu University of Health and Welfare, Miyazaki, Japan aut NATIONALLICENCE 700 1- Tsuneyoshi Isao Department of Anesthesiology, Miyazaki Medical College, University of Miyazaki, 889-1692, Miyazaki, Japan aut NATIONALLICENCE 773 0- Journal of Anesthesia Springer Japan 25/4(2011-08-01), 549-557 0913-8668 25:4<549 2011 25 540 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer