Luciferase as a model for the site of inhaled anesthetic action

The in vivo potencies of anesthetics correlate with their capacity to suppr ess the reaction of luciferin with luciferase. In addition, luciferin has s tructural resemblances to etomidate. These observations raise the issues of whether luciferin, itself, might affect anesthetic requirement, and whethe r luciferase resembles the site of anesthetic action. Because the polar luc iferin is unlikely to cross the blood-brain barrier (we found that the oliv e oil/water partition coefficient was 100 +/- 36 X 10(-7)), we studied thes e issues in rats by measuring the effect of infusion of luciferin in artifi cial cerebrospinal fluid into the lumbar subarachnoidal space and into the cerebral intraventricular space on the MAC (the minimum alveolar anesthetic concentration required to eliminate movement in response to a noxious stim ulus in 50% of tested subjects) of isoflurane. MAC in rats given lumbar int rathecal doses of luciferin estimated to greatly exceed anesthetizing doses of etomidate, did not differ significantly from MAC in rats receiving only artificial cerebrospinal fluid into the lumbar intrathecal space. MAC slig htly decreased when doses of luciferin estimated to greatly exceed anesthet izing doses of etomidate were infused intraventricularly (P < 0.05). In con trast to the absent or minimal effects of luciferin, intrathecal or intrave ntricular infusion of etomidate at similar or smaller doses significantly d ecreased isoflurane MAC. Luciferin did not affect +-aminobutyric acid type A or acetylcholine receptors expressed in Xenopus oocytes. These results su ggest that luciferin has minimal or no anesthetic effects. It also suggests that luciferin/luciferase may not provide a good surrogate for the site at which anesthetics act, if this site is on the surface of neuronal cells.