title: Contribution of α2A-adrenoceptor subtype to effect of dexmedetomidine and xylazine on spinal synaptic transmission of mice.
abstract: Alpha-2A adrenergic receptor (AR) subtype plays an important role in the analgesic effect of α2-AR agonists. Here, we examined the effects of α2-AR agonists, dexmedetomidine and xylazine, on spinal synaptic transmission in newborn C57BL/6J and α2A-AR mutant mice. Spinal reflex potentials, the monosynaptic reflex potential (MSR) and the slow ventral root potential (sVRP), were measured in isolated spinal cords. The compound action potential was measured in isolated lumbar nerve. Dexmedetomidine and xylazine suppressed both the MSR and sVRP in a concentration-dependent manner. In α2A-AR mutant mice, sVRP suppression by dexmedetomidine was greatly weakened, while that by xylazine (30-100μM) showed only slight attenuation. A high concentration (300μM) of xylazine completely suppressed the sVRP, even in α2A-AR mutant mice spinal cords, and also suppressed the compound action potential. MSR suppression by these α2-AR agonists had no difference between wild-type and α2A-AR mutant mice. These results suggest that sVRP suppression by dexmedetomidine and xylazine is mainly mediated by α2A-AR. In addition, a high concentration of xylazine inhibits conduction of the action potential, which is not mediated by α2A-AR. α2-AR is not responsible for the dexmedetomidine- and xylazine-mediated inhibition of the MSR.
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Sapporo 060-0818, Japan. Electronic address: tkobayashi@vetmed.hokudai.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Sapporo 060-0818, Japan. Electronic address: otsuguro@vetmed.hokudai.ac.jp.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Otsuguro
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Sapporo 060-0818, Japan. Electronic address: souya@vetmed.hokudai.ac.jp.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Sapporo 060-0818, Japan. Electronic address: sito@vetmed.hokudai.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ito
mesh_terms: D000200:Action Potentials; D059331:Adrenergic Neurons / Q000187:drug effects* / Q000378:metabolism; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D020927:Dexmedetomidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000172:deficiency / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D014991:Xylazine / Q000494:pharmacology*
chemical_list: C547769:Adra2a protein, mouse; C547770:Adra2a protein, rat; D058647:Adrenergic alpha-2 Receptor Agonists; D018341:Receptors, Adrenergic, alpha-2; D014991:Xylazine; D020927:Dexmedetomidine
keywords: Dexmedetomidine; Reflex potential; Spinal cord; Xylazine; α(2) Adrenoceptor