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. 2007 Jul;375(5):293-301.
doi: 10.1007/s00210-007-0168-4. Epub 2007 Jun 12.

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  1 , Kouichiro Minami, Yasuhito Uezono, Takafumi Horishita, Toru Yokoyama, Munehiro Shiraishi, Takeshi Sakurai, Akio Shigematsu, Yoichi Ueta
Affiliations

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 et al. Naunyn Schmiedebergs Arch Pharmacol. 2007 Jul.

Abstract

Dexmedetomidine, an alpha(2)-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 alpha(2)-adrenoceptor. We examined the effects of dexmedetomidine on M(1), M(3), 5-HT(2C), 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 [Ca(2+)](i) in the dorsal root ganglia (DRG) of 3-week-old Wister rats. Dexmedetomidine did not affect the 5-HT(2C)-, 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 microM)-induced Ca(2+)-activated Cl(-) currents in Xenopus oocytes expressing M(1) receptors. In contrast, dexmedetomidine inhibited the ACh-induced currents in Xenopus oocytes expressing M(3) receptors; 1 nM, 10 nM, 100 nM, and 1 microM 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 (EC(50) = 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 [Ca(2+)](i) in cultured DRG cells in a concentration-dependent manner. Dexmedetomidine inhibits the function of M(3) receptors, in addition to its agonistic effects on alpha(2)-adrenoceptors, which provides further insight into the pharmacological properties of dexmedetomidine.

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References

    1. J Physiol. 1999 Jan 15;514 ( Pt 2):351-67 - PubMed
    1. Brain Res. 1990 Mar 12;511(1):71-9 - PubMed
    1. Naunyn Schmiedebergs Arch Pharmacol. 2005 Mar;371(3):221-8 - PubMed
    1. Anesth Analg. 2001 Aug;93(2):375-81 , 3rd contents page - PubMed
    1. Curr Top Med Chem. 2002 Jun;2(6):507-28 - PubMed

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