In 1951 Folch and Lees described the presence in brain tissue of a protein material insoluble in water and aqueous solvents and soluble in chloroform: methanol mixtures. Since all other known proteins were completely insoluble in these solvent mixtures, it was assumed that the proteins involved were combined with a lipid moiety that gave the complex its particular lipidlike solubility. To designate this new type of substances, they coined the term proteolipid to indicate that they were lipoproteins with some of the physical properties of lipids, in sharp contrast to other then known lipoproteins which were soluble in water and aqueous solutions and, not only insoluble in chloroform:methanol, but usually rendered insoluble in water (“denatured”) by exposure to this particular solvent mixture. Subsequent work (which is discussed below) showed that proteolipids are general tissue constituents usually associated with membranous structures and that, in addition to their unusual solubility properties, they are characterized by resistance to most proteolytic enzymes and by a pattern of amino acid composition that may vary according to the source of the proteolipid but retains throughout the group some special characteristics.

Proteolipids from membrane systems

Stereospecific binding of narcotics to brain cerebrosides

A proteolipid isolated from a lipid extract of mouse brain demonstrates stereospecific binding properties for levorphanol. It is present only in neuronal tissue and most abundant in the rhombencephalon. One component saturates at a concentration corresponding to maximum pharmacologic effect in vivo. The estimated mass is 60,000 daltons per bound opiate molecule.

Partial Purification of an Opiate Receptor from Mouse Brain

—In vitro binding experiments with 5-hydroxy[14C]tryptamine (3.3 × 10−6 M) were carried out on subcellular fractions of the cat brain. The highest specific activity was observed in some fractions of nerve-ending membranes isolated from the hypothalamus, basal ganglia, and gray areas of the mesencephalon. The specificity of this high affinity binding was demonstrated by competition with reserpine, butanolamide of lysergic acid, and desmethylimipramine. With butanol-water extraction the [14C]5-HT was found in the butanol while the gangliosides were separated in the water phase. Several experiments with thin layer and column chromatography suggest that in the organic phase the [14C]5-HT is not bound to the lipids but to a special proteolipid. This proteolipid is different from that found in myelin and has similar chromatographic properties to that previously observed in the proteolipid which binds d-[14C]tubocurarine in nerve-ending membranes of the cerebral cortex.

Renée Plácido

Papers

Fractionation of lipids and proteolipids from cat grey and white matter by chromatography on an organophilic dextran gel