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Inhibition of LCAT in plasma from man and experimental animals by chlorpromazine

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Lipids

Abstract

Chlorpromazine (CPZ), a major tranquilizer, was found to be a potent inhibitor of lecithin:cholesterol acyltransferase (LCAT, EC 2.3.1.43) in the plasma of normal man, rat, rabbit and dog in vitro. The inhibitory effect of CPZ reached 35–50% at 0.5 mM depending on species; dog plasma LCAT appeared to be somewhat more sensitive than that of the other species. In rats fed CPZ or lidocaine for 14 days (0.05% in the diet), there was no statistically significant change in total plasma cholesterol levels or the size of the plasma-free (unesterified) cholesterol pool. However, 5 hr after an intracardial injection of [14C] cholesterol, the percentage of plasma [14C] cholesterol that was esterified was significantly lower (ca. 6%, p<0.05) in the CPZ-treated group, suggesting that CPZ may also inhibit LCAT to some extent in vivo. The percentage of plasma [14C] cholesterol esterified in the lidocainetreated group was similar to control values and did not reflect its ability to inhibit LCAT in vitro.

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References

  1. Sugano, M., and Portman, O.W. (1965) Arch. Biochem. Biophys. 109, 302–315.

    Article  CAS  Google Scholar 

  2. Glosmet, J.A., Janssen, E.T., Kennedy, R., and Dobbins, J. (1966) J. Lipid Res. 7, 638–648.

    Google Scholar 

  3. Fielding, C.J., and Fielding, P.E. (1971) FEBS Lett. 15, 355–358.

    Article  PubMed  CAS  Google Scholar 

  4. Bell, F.P., and Hubert, E.V. (1980) Lipids 15, 811–814.

    PubMed  CAS  Google Scholar 

  5. Piran, U., and Nishida, T. (1976) J. Biochem. 80, 887–889.

    PubMed  CAS  Google Scholar 

  6. Aron, L., Jones, S., and Fielding, C.J. (1978) J. Biol. Chem. 253, 7220–7226.

    PubMed  CAS  Google Scholar 

  7. Piran, U., and Nishida, T. (1979) Lipids 14, 478–482.

    Article  PubMed  CAS  Google Scholar 

  8. Seeman, P. (1972) Pharmacol. Rev. 24, 583–655.

    PubMed  CAS  Google Scholar 

  9. Bickel, M.H. (1975) J. Pharm. Pharmac. 27, 733–738.

    CAS  Google Scholar 

  10. Rehnborg, C.S., and Nichols, A.V. (1964) Biochim. Biophys. Acta 84, 596–603.

    PubMed  CAS  Google Scholar 

  11. Nichols, A.V., and Smith, L. (1965) J. Lipid Res. 6, 206–210.

    PubMed  CAS  Google Scholar 

  12. Glosmet, J.A., Norum, K.R., Nichols, A.V., Forte, T., King, W.C., Albers, J.J., Mitchell, C.D., Applegate, K.R., and Gjone, E. (1974) Scand. J. Clin. Lab. Invest. (Suppl. 137) 33, 165–171.

    Google Scholar 

  13. Bell, F.P., and Schwartz, C.J. (1971) Biochim. Biophys. Acta 231, 553–557.

    PubMed  CAS  Google Scholar 

  14. Stokke, K.T., and Norum, K.R. (1971) Scand. J. Clin. Lab. Invest. 27, 21–27.

    PubMed  CAS  Google Scholar 

  15. Lacko, A.G., Rutenberg, H.L., and Soloff, L.A. (1973) Biochem. Med. 7, 178–183.

    Article  PubMed  CAS  Google Scholar 

  16. Bell, F.P. (1976) Exp. Mol. Pathol. 25, 279–292.

    Article  PubMed  CAS  Google Scholar 

  17. Bell, F.P., Lofland, H.B., and Stokes, N.A. (1970) Atherosclerosis 11, 235–246.

    Article  PubMed  CAS  Google Scholar 

  18. Block, W.D., Jarrett, K.J., and Lewis, J.B. (1966) Clin. Chem. 12, 681–689.

    PubMed  CAS  Google Scholar 

  19. Sperry, W.M., and Webb, M. (1950) J. Biol. Chem. 187, 97–106.

    PubMed  CAS  Google Scholar 

  20. Papahadjopoulos, D., Jacobson, K., Poste, G., and Shepherd, G. (1975) Biochim. Biophys. Acta 394, 504–519.

    Article  PubMed  CAS  Google Scholar 

  21. Scherphof, G., and Westernberg, G. (1975) Biochim. Biophys. Acta 398, 442–451.

    PubMed  Google Scholar 

  22. Bowley, M., Cooling, J., Burditt, S.L., and Brindley, D.N. (1977) Biochem. J. 165, 447–454.

    PubMed  CAS  Google Scholar 

  23. Neal, M.J., Butler, K.W., Polnaszek, C.F., and Smith, I.C.P. (1976) Molec. Pharmacol. 12, 144–155.

    CAS  Google Scholar 

  24. Lee, A.G. (1977) Molec. Pharmacol. 13, 474–487.

    CAS  Google Scholar 

  25. Jain, M.K., Eskow, K., Kuchibhotla, J., and Colman, R.W. (1978) Thromb. Res. 13, 1067–1075.

    Article  PubMed  CAS  Google Scholar 

  26. Keefe, E.B., Blankenship, N.M., and Scharschmidt, B.F. (1980) Gastroenterology 79, 222–231.

    Google Scholar 

  27. Yokoyama, S., Fukushima, D., Kupferberg, J.P., Kezdy, F.J., and Kaiser, E.T. (1980) J. Biol. Chem. 255, 7333–7339.

    PubMed  CAS  Google Scholar 

  28. Glosmet, J.A. (1979) Prog. Biochem. Pharmacol. 15, 41–66.

    Google Scholar 

  29. Clark, M.L., Ray, T.S., Paredes, A., Ragland, R.E., Costiloe, J.P., Smith, C.W., and Wolf, S. (1967) Psychosomat. Med. 29, 634–642.

    CAS  Google Scholar 

  30. Clark, M., Dubowski, K., and Colmore, J. (1970) Clin. Pharmacol. Therapeut. 11, 883–889.

    CAS  Google Scholar 

  31. Boyes, R.N., Scott, D.B., Jebson, P.J., Godman, J.J., and Julian, D.J. (1971) Clin. Pharmacol. Ther. 12, 105–116.

    PubMed  CAS  Google Scholar 

  32. Rowland, M., Thompson, P.D., Guichard, A., and Melmon, K.L. (1971) Ann. N.Y. Acad. Sci. 179, 383–398.

    PubMed  CAS  Google Scholar 

  33. Efron, D.H., Harris, S.R., Manian, A.A., and Gaudette, L.E. (1971) Psychopharmacologia 19, 207–223.

    Article  PubMed  CAS  Google Scholar 

  34. VanLoon, E.J., Flanagan, T.L., Novick, W.J., and Maass, A.R. (1964) J. Pharm. Sci. 53, 1211–1213.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Diabetes and Atherosclerosis Research, The Upjohn Company, 49001, Kalamazoo, MI

    Frank P. Bell & Edna V. Hubert

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  1. Frank P. Bell
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  2. Edna V. Hubert
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Bell, F.P., Hubert, E.V. Inhibition of LCAT in plasma from man and experimental animals by chlorpromazine. Lipids 16, 815–819 (1981). https://doi.org/10.1007/BF02535035

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  • DOI: https://doi.org/10.1007/BF02535035

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