Dexmedetomidine inhibits muscarinic type 3 receptors expressed in Xenopus oocytes and muscarine-induced intracellular Ca2+ elevation in cultured rat dorsal root ganglia cells

  • Atsushi Takizuka
  • Kouichiro Minami
  • Yasuhito Uezono
  • Takafumi Horishita
  • Toru Yokoyama
  • Munehiro Shiraishi
  • Takeshi Sakurai
  • Akio Shigematsu
  • Yoichi Ueta
Original Article


Dexmedetomidine, an α2-adrenoceptor agonist, has been approved for clinical use, although the mechanism of dexmedetomidine action has not been fully elucidated. Several studies have shown that G protein-coupled receptors (GPCRs) are recognized as targets for anesthetics and analgesics. Therefore, it is of interest to determine whether dexmedetomidine affects the function of GPCRs other than the α2-adrenoceptor. We examined the effects of dexmedetomidine on M1, M3, 5-HT2C, substance P, and orexin 1 receptors in Xenopus oocytes expressing individual receptors. In addition, we investigated the effects of dexmedetomidine on muscarinic receptor-mediated changes in [Ca2+]i in the dorsal root ganglia (DRG) of 3-week-old Wister rats. Dexmedetomidine did not affect the 5-HT2C-, or substance P-induced Cl currents and had little inhibition on the orexin A-induced current in oocytes expressing the respective receptors. The compound also had little effect on the acetylcholine (ACh, 1 μM)-induced Ca2+-activated Cl currents in Xenopus oocytes expressing M1 receptors. In contrast, dexmedetomidine inhibited the ACh-induced currents in Xenopus oocytes expressing M3 receptors; 1 nM, 10 nM, 100 nM, and 1 μM dexmedetomidine reduced the current to 66.5 ± 4.8, 51.3 ± 12, 34.6 ± 11, and 26.8 ± 6.4% of the control value, respectively (EC50 = 3.5 ± 0.7 nM). Dexmedetomidine reduced the ACh-induced Cl currents after treatment with the selective protein kinase C inhibitor GF109203X. Moreover, the compound inhibited the muscarinic receptor-mediated increases in [Ca2+]i in cultured DRG cells in a concentration-dependent manner. Dexmedetomidine inhibits the function of M3 receptors, in addition to its agonistic effects on α2-adrenoceptors, which provides further insight into the pharmacological properties of dexmedetomidine.


Dexmedetomidine M3 receptors Xenopus oocytes Dorsal root ganglia 


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Atsushi Takizuka
    • 1
  • Kouichiro Minami
    • 2
    • 3
    • 4
  • Yasuhito Uezono
    • 5
  • Takafumi Horishita
    • 1
  • Toru Yokoyama
    • 4
  • Munehiro Shiraishi
    • 1
  • Takeshi Sakurai
    • 6
  • Akio Shigematsu
    • 7
  • Yoichi Ueta
    • 4
  1. 1.Department of Anesthesiology, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan
  2. 2.Department of Anesthesiology and Critical Care MedicineJichi Medical UniversityTochigiJapan
  3. 3.Emergency Life-Saving Technique Academy of Tokyo (ELSTA TOKYO)TokyoJapan
  4. 4.Department of Physiology, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan
  5. 5.Department of PharmacologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  6. 6.Department of Molecular Pharmacology, Graduation School of Comprehensive Human SciencesUniversity of TsukubaTsukubaJapan
  7. 7.School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan

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