Abstract
A new kind of pharmacologic activity called hypobetalipoproteinemia is described. Operationally the activity consists of a marked reduction of heparin precipitating lipoproteins (beta and/or pre-beta electrophoretic mobility) in hypercholesterolemic animals with a simultaneous decrease in the heparin precipitating lipoprotein:cholesterol ratio. As determined by ultracentrifugal fractionation of the lipoproteins from hypercholesterolemic rat serum, this activity consists of both a reduction in heparin precipitating lipoproteins and an increase in high density lipoproteins that are not precipitated by heparin. Changes in composition were also induced in both lipoprotein fractions. The greatest changes were observed for free and esterified cholesterol, which were markedly reduced in the heparin precipitating lipoproteins and concomitantly increased in the high density lipoproteins. The hypobetalipoproteinemic agent exhibiting this activity is 1-[p-(1′-adamantyloxy)phenyl]-piperidine (U-41792). This agent is active in hypercholesterolemic rats, mice, quail, and pigeons.
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References
Burstein, M. and H.R. Scholnick. 1973. Lipoprotein-polyanionmetal interactions. In Advances in Lipid Research, ed. by R. Paoletti and D. Kritchevsky, Academic Press, New York, pp. 68–108.
Schurr, P.E., J.R. Schultz, and CE. Day. 1976. High volume screening procedures for hypolipoproteinemic activity in rats. In Atherosclerosis Drug Discovery, ed. by C.E. Day, Plenum Press, New York, pp. 215–229.
Day, C.E., P.E. Schurr, D.E. Emmert, R.E. Ten Brink, and D. Lednicer. 1975. Hypobetalipoproteinemic agents. I. Bicyclo [2.2.2]octyloxyaniline and its derivatives. J. Med. Chem. 18: 1065–1070.
Block, W.D., K.J. Jarrett, Jr., and J.B. Levine. 1965. Use of a single color reagent to improve the automated determination of serum total cholesterol. In Automation in Analytical Chemistry, ed. by L.T. Skeggs, Jr., Mediad Inc., New York, pp. 345–347.
Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.
Abell, L.L., B.B. Levr, B.B. Brodie, and F.E. Kendall. 1952. A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J. Biol. Chem. 195:357–367.
Mills, G.L. and C.E. Taylaur. 1971. The distribution and composition of serum lipoproteins in eighteen animals. Comp. Biochem. Physiol. 40B:489–501.
Royer, M.E. and H. Ko. 1969. A simplified semi-automated assay for plasma triglycerides. Anal. Biochem. 29:405–416.
Stewart, C.P. and E.B. Hendry. 1935. The phospholipids of blood. Biochem. J. 29 1683–1689.
Steel, R.G.D. and J.H. Torrie. 1960. Principles and Procedures of Statistics, McGraw-Hill, New York, p. 106.
Tennent, D.M., H. Siegel, G.W. Kuron, W.H. Ott, and C.W. Mushett. 1957. Lipid patterns and atherogenesis in cholesterol fed chickens. Proc. Soc. Exptl. Biol. Med. 96:679–683.
Day, C.E., B. Barker, and W.W. Stafford. 1974. Composition of very low density lipoproteins from cholesterol fed animals. Comp. Biochem. Physiol. 49B:501–505.
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Day, C.E., Schurr, P.E., Heyd, W.E., Lednicer, D. (1976). Biological Activity of a Hypobetalipoproteinemic Agent. In: Day, C.E. (eds) Atherosclerosis Drug Discovery. Advances in Experimental Medicine and Biology, vol 67. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4618-7_14
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DOI: https://doi.org/10.1007/978-1-4614-4618-7_14
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