Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Aug;84(16):5972–5975. doi: 10.1073/pnas.84.16.5972

General anesthetics can competitively interfere with sensitive membrane proteins.

P W Tas, H G Kress, K Koschel
PMCID: PMC298985  PMID: 3475715

Abstract

It is not known whether proteins or lipids are the primary target of anesthetic action. The resolution of this problem is hampered by the fact that it is not possible to investigate the biological activity of integral membrane proteins in the absence of lipids. However, certain characteristics of membrane protein function inhibition by anesthetics cannot be explained on the basis of an indirect inhibition by disturbance of the lipid bilayer and, therefore, most likely are the result of a direct anesthetic-protein interaction. This is the case (i) when the anesthetics competitively interfere with the binding of an endogenous ligand to the membrane protein and (ii) when the size of the anesthetic molecule is of importance for the potency and/or mechanism of inhibition. The present study shows that this is true for a membrane transport system, the Na+/K+/Cl- cotransport in glial-type cells.

Full text

PDF
5972

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benda P., Lightbody J., Sato G., Levine L., Sweet W. Differentiated rat glial cell strain in tissue culture. Science. 1968 Jul 26;161(3839):370–371. doi: 10.1126/science.161.3839.370. [DOI] [PubMed] [Google Scholar]
  2. Bourke R. S., Nelson K. M. Further studies on the K + -dependent swelling of primate cerebral cortex in vivo: the enzymatic basis of the K + -dependent transport of chloride. J Neurochem. 1972 Mar;19(3):663–685. doi: 10.1111/j.1471-4159.1972.tb01383.x. [DOI] [PubMed] [Google Scholar]
  3. Epstein F. H., Silva P. Na-K-Cl cotransport in chloride-transporting epithelia. Ann N Y Acad Sci. 1985;456:187–197. doi: 10.1111/j.1749-6632.1985.tb14864.x. [DOI] [PubMed] [Google Scholar]
  4. Forbush B., 3rd, Palfrey H. C. [3H]bumetanide binding to membranes isolated from dog kidney outer medulla. Relationship to the Na,K,Cl co-transport system. J Biol Chem. 1983 Oct 10;258(19):11787–11792. [PubMed] [Google Scholar]
  5. Franks N. P., Lieb W. R. Do general anaesthetics act by competitive binding to specific receptors? Nature. 1984 Aug 16;310(5978):599–601. doi: 10.1038/310599a0. [DOI] [PubMed] [Google Scholar]
  6. Geck P., Pfeiffer B. Na+ + K+ + 2Cl- cotransport in animal cells--its role in volume regulation. Ann N Y Acad Sci. 1985;456:166–182. doi: 10.1111/j.1749-6632.1985.tb14862.x. [DOI] [PubMed] [Google Scholar]
  7. Hannafin J., Kinne-Saffran E., Friedman D., Kinne R. Presence of a sodium-potassium chloride cotransport system in the rectal gland of Squalus acanthias. J Membr Biol. 1983;75(1):73–83. doi: 10.1007/BF01870801. [DOI] [PubMed] [Google Scholar]
  8. Johnson J. H., Dunn D. P., Rosenberg R. N. Furosemide-sensitive K+ channel in glioma cells but not neuroblastoma cells in culture. Biochem Biophys Res Commun. 1982 Nov 16;109(1):100–105. doi: 10.1016/0006-291x(82)91571-6. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. McCreery M. J., Hunt W. A. Physico-chemical correlates of alcohol intoxication. Neuropharmacology. 1978 Jul;17(7):451–461. doi: 10.1016/0028-3908(78)90050-3. [DOI] [PubMed] [Google Scholar]
  11. McRoberts J. A., Erlinger S., Rindler M. J., Saier M. H., Jr Furosemide-sensitive salt transport in the Madin-Darby canine kidney cell line. Evidence for the cotransport of Na+, K+, and Cl-. J Biol Chem. 1982 Mar 10;257(5):2260–2266. [PubMed] [Google Scholar]
  12. Richards C. D., Martin K., Gregory S., Keightley C. A., Hesketh T. R., Smith G. A., Warren G. B., Metcalfe J. C. Degenerate perturbations of protein structure as the mechanism of anaesthetic action. Nature. 1978 Dec 21;276(5690):775–779. doi: 10.1038/276775a0. [DOI] [PubMed] [Google Scholar]
  13. Steward A., Allott P. R., Cowles A. L., Mapleson W. W. Solubility coefficients for inhaled anaesthetics for water, oil and biological media. Br J Anaesth. 1973 Mar;45(3):282–293. doi: 10.1093/bja/45.3.282. [DOI] [PubMed] [Google Scholar]
  14. Tas P. W., Kress H. G., Koschel K. Halothane inhibits the neurotoxin stimulated [14C]guanidinium influx through 'silent' sodium channels in rat glioma C6 cells. FEBS Lett. 1985 Mar 25;182(2):269–272. doi: 10.1016/0014-5793(85)80313-6. [DOI] [PubMed] [Google Scholar]
  15. Tas P. W., Massa P. T., Koschel K. Preliminary characterization of an Na+,K+,Cl- co-transport activity in cultured human astrocytes. Neurosci Lett. 1986 Oct 20;70(3):369–373. doi: 10.1016/0304-3940(86)90581-1. [DOI] [PubMed] [Google Scholar]
  16. Wishnia A., Pinder T. W., Jr Hydrophobic interactions in proteins. The alkane binding site of beta-lactoglobulins A and B. Biochemistry. 1966 May;5(5):1534–1542. doi: 10.1021/bi00869a013. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES