Structure activity relationship of cholesterol and steroid hormones with respect to their effects on the Ca2+-stimulated ATPase and lipid fluidity of synaptosomal plasma membranes from dog and rabbit brain.
1. Binding of liposomal-[14C]-cholesterol into dog brain synaptosomal plasma membranes (SPM) follows a sigmoid path (Hill coefficient h = 1.96 +/- 0.12). 2. Ca2+-stimulated ATPase activity increased (approx. 95%) at a concentration range (0.1-0.4 mM) of liposomal cholesterol and testosterone (up to 10 microM). While progesterone up to 10 microM decreased the enzyme activity (approx. 70%) in dog and rabbit brain SPM. 3. Fluorescence anisotropy, [(r0/r)-1]-1, of 1,6-diphenyl-1,3,5-hexatriene (DPH) was 1.04 +/- 0.04 in rabbit brain SPM and 1.72 +/- 0.09 in dog brain SPM. 4. Lipid phase separations at 23.5 +/- 1.2 degrees C in dog brain SPM and at 17.2 +/- 0.9 degrees C in rabbit brain SPM were observed. In dog brain SPM it increased to 33.4 +/- 1.8 degrees C, while in rabbit brain SPM was abolished after treatment with liposomal cholesterol. 5. The allosteric inhibition of Ca2+-stimulated ATPase by Na+ ions showed a Hill coefficient h = 1.72 +/- 0.15 and h = 1.48 +/- 0.08 for dog and rabbit brain SPM respectively, which increased to h = 2.83 +/- 0.55 and h = 2.34 +/- 0.35 after treatment with liposomal cholesterol.
Deliconstantinos
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Department of Experimental Physiology, University of Athens Medical School, Greece.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D005454:Fluorescence Polarization; D066298:In Vitro Techniques; D007700:Kinetics; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D011817:Rabbits; D013256:Steroids / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D008563:Membrane Lipids; D013256:Steroids; D002784:Cholesterol; D000252:Calcium-Transporting ATPases