English
TitleMolecular Genetic Technology Defines the Receptor Subtypes Responsible for Anesthetic and Cardiovascular Responses to alpha-2 Adrenergic Agonists
Subtitle
AuthorsToshiki Mizobe*1, Takahiko Kamibayashi*2, Guo Tianzhi*2, Katsumi Harasawa*2, Mervyn Maze*2
Authors(kana)
Organization*1Department of Anesthesiology, Kyoto Prefectural University of Medicine, *2Departments of Anesthesia, VAPAHCS and Stanford University School of Medicine
JournalCirculation Control
Volume19
Number1
Page89-95
Year/Month1998/
ArticleOriginal article
PublisherJapan Society of Circulation Control
Abstract[Abstract] The analgesic effects of ƒ¿2 adrenergic agonists are mediated by activation of ƒ¿2 adrenoceptor in the locus coeruleus (LC) and spinal cord (SC). It is not known which of the three ƒ¿2 adrenoceptor subtypes is responsible for the analgesic effects. Using a genetargeting strategy, it is possible to determine their role in the analgesic action of dexmedetomidine, an ƒ¿2 agonist. The guide cannulae were sited stereotactically in the LC or intrathecally in male Sprague-Dawley rats. The antinociceptive effect of dexmedetomidine was measured using the tail flick latency (TFL) response. Separate cohorts of rats were administered the ODNs directed against either the ƒ¿2A or ƒ¿2c adrenoceptor subtypes which are present in the CNS. Control rats were treated with scrambled ODNs or saline. The TFL response to dexmedetomidine was measured, before, immediately after, and 8 days after the ODN administration. Immediately following ƒ¿2A ODN treatment, the TFL response to dexmedetomidine, either LC or SC, was significantly attenuated ; this recovered to the pretreatment value after 8 days. ƒ¿2c ODN treatment did not change the analgesic response. The analgesic response to morphine was unaffected by ƒ¿2A ODN treatment. These data strongly suggest that the ƒ¿2A adrenoceptor subtype mediates the analgesic responses to dexmedetomidine both in the LC and in the SC.
PracticeBasic medicine
KeywordsAdrenoceptor, ƒ¿2 adrenergic agonists, Analgesia, Dexmedetomidine

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