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Enflurane inhibits the function of mouse and human brain phosphatidylinositol-linked acetylcholine and serotonin receptors expressed in Xenopus oocytes

LH Lin, S Leonard and RA Harris

Department of Pharmacology, University of Colorado Health Sciences Center, Denver.

Modulation of the inositol 1,4,5-trisphosphate (IP3)-mediated signal transduction pathway by the inhalational anesthetic enflurane was studied in Xenopus oocytes expressing mouse and human cortical mRNA. We found that enflurane significantly inhibited ion currents activated by m1 muscarinic and 5-hydroxytryptamine (5-HT)1c receptors. This inhibition was dependent upon the concentration of acetylcholine or 5- HT, with large inhibition (80-89%) of low concentrations and small inhibition (8-44%) of high concentrations of acetylcholine and 5-HT. Similar effects were found with either mouse or human receptors. To investigate the mechanism of enflurane action, ion currents induced by intracellular injection of guanosine 5'-(3-O-thio)triphosphate and IP3 were examined. Enflurane strongly suppressed the guanosine 5'-(3-O- thio)triphosphate-activated current but not the IP3-activated current. These results suggest that an inhalational anesthetic can disrupt the function of mouse and human brain phosphatidylinositol-linked receptors by selectively inhibiting the guanine nucleotide-binding protein activity.

Volume 43, Issue 6, pp. 941-948, 06/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics




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