Effects of polyhydric and monohydric compounds on the stability of type I receptors for adrenal steroids in brain cytosol.
We have shown previously that unoccupied type I receptors for adrenal steroids in brain cytosol lose their capacity to bind [3H]aldosterone ([3H]ALDO) in a time- and temperature-dependent manner. Based on reports that sugars and polyvalent alcohols are capable of stabilizing a variety of globular proteins, we attempted in the present study to stabilize type I receptors by including polyhydric compounds in our brain cytosol preparations. However, contrary to expectations, adjusting cytosol to a 10% (g/dl) concentration of ethylene glycol, glycerol, erythritol, xylitol, ribitol, or sorbitol failed to stabilize these receptors at 0 degree C and in fact produced a slight reduction in [3H]ALDO binding capacity. The magnitude of this reduction was greater when cytosol was incubated for 2 h at 22 degrees C prior to incubation with [3H]ALDO. In contrast to these results, when brain cytosol was adjusted to a 10% (g/dl) concentration of the monohydric compound, ethanol, a significant increase in [3H]ALDO binding to type I receptors was found. Under identical conditions, methanol and propanol failed to have a significant effect on the binding capacity of these receptors. When cytosol was aged for 2 h at 22 degrees C, all three of these monohydric compounds produced a marked loss in the [3H]ALDO binding capacity of type I receptors. An investigation of various doses of ethanol at 0 degree C on the subsequent binding of [3H]ALDO yielded an inverse U-shaped curve with 10% ethanol producing the highest level of specific binding, as reflected by an increase in maximal binding in Scatchard plots, and 40% ethanol producing a complete loss in type I receptor binding capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
Emadian
S M
SM
Department of Neuroscience, University of Florida, College of Medicine, Gainesville 32610.
Luttge
W G
WG
D000433:1-Propanol / Q000494:pharmacology; D000438:Alcohols / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004896:Erythritol / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D019855:Ethylene Glycol; D005026:Ethylene Glycols / Q000494:pharmacology; D005260:Female; D005990:Glycerol / Q000494:pharmacology; D000432:Methanol / Q000494:pharmacology; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid; D012255:Ribitol / Q000494:pharmacology; D013012:Sorbitol / Q000494:pharmacology; D014993:Xylitol / Q000494:pharmacology
D000438:Alcohols; D005026:Ethylene Glycols; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000431:Ethanol; D012255:Ribitol; D000450:Aldosterone; D013012:Sorbitol; D000433:1-Propanol; D019855:Ethylene Glycol; D005990:Glycerol; D004896:Erythritol; D014993:Xylitol; D000432:Methanol