This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Huang, Y.-H. Articles by Huang, C.-J. Search for Related Content PubMed PubMed Citation Articles by Huang, Y.-H. Articles by Huang, C.-J.

---

ANESTHETIC PHARMACOLOGY

Lidocaine Inhibition of Inducible Nitric Oxide Synthase and Cationic Amino Acid Transporter-2 Transcription in Activated Murine Macrophages May Involve Voltage-Sensitive Na⁺ Channel

Departments of Anesthesiology and Medical Research, Mackay Memorial Hospital; Mackay Medicine, Nursing and Management College; College of Nursing and Graduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan

Address correspondence and reprint requests to Chun-Jen Huang, MD, PhD, Department of Anesthesiology, Mackay Memorial Hospital, 92, Sec. 2 Chung San N. Rd., Taipei 10449, Taiwan. Address e-mail to sean{at}ms2.mmh.org.tw.

Lidocaine has been reported to inhibit nitric oxide (NO) production in activated murine macrophages, but the role of inducible NO synthase (iNOS) in lidocaine-induced inhibition of NO has not been explored. In addition, type-2 cationic amino acid transporter (CAT-2) and guanosine triphosphate cyclohydrolase I (GTPCH) also regulate iNOS activity. The effects of lidocaine on CAT-2 and GTPCH are unknown. To explore further these effects, confluent immortalized murine macrophages (RAW264.7 cells) were incubated with lipopolysaccharide (LPS) or in combination with lidocaine (5, 50, or 500 µM) for 18 h before harvesting. We also used tetrodotoxin (TTX) and veratridine to elucidate the possible role of voltage-sensitive Na⁺ channel. Our data demonstrated that LPS significantly upregulated transcription of iNOS and CAT-2 but not GTPCH in stimulated macrophages. In a dose-dependent manner, lidocaine significantly attenuated the LPS-induced upregulation of iNOS and CAT-2. Conversely, lidocaine significantly increased GTPCH transcription in LPS-stimulated macrophages. The effects of TTX on iNOS, CAT-2, and GTPCH expression were comparable to those of lidocaine. In addition, veratridine significantly attenuated the effects of lidocaine and TTX. We therefore concluded that lidocaine significantly inhibits iNOS and CAT-2 and, in turn, enhances GTPCH transcription in LPS-stimulated macrophages via a mechanism that possibly involves the voltage-sensitive Na⁺ channel.