Role of Pertussis Toxin-sensitive G-Proteins in the Analgesic and Anesthetic Actions of α2-Adrenergic Agonists in the Rat
Open Access
- 1 October 1995
- journal article
- laboratory investigations
- Published by Wolters Kluwer Health in Anesthesiology
- Vol. 83 (4) , 816-822.
- https://doi.org/10.1097/00000542-199510000-00022
Abstract
Background: alpha 2 Adrenoceptors are coupled to G-proteins sensitive to pertussis toxin (PTX) in the locus coeruleus. At this site, the hypnotic response to dexmedetomidine, an alpha 2 agonist, can be blocked by pretreatment with PTX. G-proteins sensitive to PTX may also be involved in the transduction of anesthetic and analgesic responses to alpha 2 agonists at supraspinal or spinal sites. To address this question the effects of pretreatment with PTX administered intracerebroventricularly, intrathecally, or a combination of the two were examined on the MAC for halothane, and the anesthetic-sparing and analgesic effects of a systemically administered alpha 2 agonist, dexmedetomidine. Methods: Rats were cannulated intracerebroventricularly, intrathecally, and with a combination of intracerebroventricular/intrathecal and treated with PTX (0 and 2.5 micrograms intracerebroventricularly; 0 or 0.5 microgram intrathecally; 0 + 0 or 2.5 + 0.5 intracerebroventricular-intrathecal)). After 7 days, either the analgesic (tail-flick latency) or the MAC-sparing effects of a calculated 50% effective dose of dexmedetomidine were measured. To confirm that intracerebroventricularly administered PTX was effective, ribosylation of G-proteins was assessed in periventricular brain tissue. Results: The analgesic action of dexmedetomidine was blocked by PTX intrathecally but not by PTX via the intracerebroventricular route. The MAC-sparing action of dexmedetomidine was not blocked by PTX via the intrathecal or intracerebroventricular routes alone or in combination. Yet, intracerebroventricularly administered PTX effectively ribosylated the G-proteins. Conclusions: Taken together with the authors' previous report, these data suggest that the hypnotic and the analgesic responses to dexmedetomidine are transduced via PTX-sensitive G-protein-coupled alpha 2 adrenoceptors but at separate sites (analgesic-spinal; hypnotic-locus coeruleus). Further studies are needed to localize the precise site(s) for the MAC-sparing effect of dexmedetomidine and to establish whether PTX-sensitive G-proteins are involved in this response.Keywords
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