1. Rat cerebral cortical synaptoneurosomal membranes. Structure and interactions with imidazobenzodiazepine and 1,4-dihydropyridine calcium channel drugs.
- Author
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Moring J, Shoemaker WJ, Skita V, Mason RP, Hayden HC, Salomon RM, and Herbette LG
- Subjects
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester metabolism, Animals, Cell Membrane metabolism, Cell Membrane ultrastructure, Cerebral Cortex metabolism, Flumazenil metabolism, Microscopy, Electron, Models, Molecular, Myelin Basic Protein analysis, Neurons metabolism, Nimodipine metabolism, Protein Conformation, Rats, Receptors, Cholinergic metabolism, Receptors, GABA-A metabolism, Ryanodine Receptor Calcium Release Channel, Synaptosomes metabolism, X-Ray Diffraction, Anti-Anxiety Agents metabolism, Calcium Channel Blockers metabolism, Cerebral Cortex ultrastructure, Dihydropyridines metabolism, Neurons ultrastructure, Receptors, Cholinergic ultrastructure, Receptors, GABA-A ultrastructure, Synaptosomes ultrastructure
- Abstract
Small angle x-ray scattering has been used to investigate the structure of synaptoneurosomal (SNM) membranes from rat cerebral cortex. Electron micrographs of the preparation showed SNM with classical synaptic appositions intact, other vesicles, occasional mitochondria, and some myelin. An immunoassay for myelin basic protein placed the myelin content of normal rat SNM at less than 2% by weight of the total membrane present. X-Ray diffraction patterns showed five diffraction orders with a unit cell repeat for the membrane of 71 to 78 A at higher hydration states. At lower hydration, 11 orders appeared; the unit cell repeat was 130 A, indicating that the unit cell contained two membranes. Electron density profiles for the 130-A unit cell were determined; they clearly showed the two opposed asymmetrical membranes of the SNM vesicles. SNM membrane/buffer partition coefficients (Kp) of imidazobenzodiazepine and 1,4-dihydropyridine (DHP) calcium channel drugs were measured; Kp's for DHP drugs were approximately five times higher in rabbit light sarcoplasmic reticulum than in SNM. Ro 15-1788 and the DHP BAY K 8644 bind primarily to the outer monolayer of vesicles of intact SNM membranes. Nonspecific equilibrium binding of Ro 15-1788 occurs mainly in the upper acyl chain of the bilayer in lipid extracts of SNM membrane.
- Published
- 1990
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