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Biomedical subjects

R R Almon

Publications and source records attributed to R R Almon.

46 records · Page 3Linked to original sources
PubMed1975

Interaction of myasthenic serum globulin with the acetylcholine receptor.

A serum factor from patients with myasthenia gravis which inhibited the binding of 125I-labeled alpha-bungarotoxin to acetylcholine receptor extracted with Triton X-100 from rat muscle has been studied in detail. The inhibitory activity was localized to the IgG fraction based upon the fractionations by sodium sulfate precipitation and DEAE chromatography as well as reaction with anti-IgG globulin. The myasthenic globulin inhibited toxin binding to receptors extracted from degenerated muscle but did not inhibit toxin binding to normal junctional receptors. At saturation levels of myasthenic globulin, the number of denervated acetylcholine receptors available for toxin binding was reduced approx. 50 percent. The myastehnic globulin was found to bind to denervated acetylcholine receptors but not to normal acetylcholine receptors by a radioimmunoassay technique in which myasthenic globulin incubated with 125I-labeled alpha bungarotoxin-receptor complexes was precipitated by anti-IgG serum. The globulin binding was saturable over the same range as inhibition of toxin binding. The data suggest that the myasthenic IgC binds to a site on the receptor complex juxtaposed to the acetylcholine receptor site. The myasthenic globulin appears to be a useful probe for investigation differences between acetylcholine receptors extracted from normal and denervated muscle and for investigating the pathogenesis of myasthenia gravis.

Acetylcholine↗
PubMed1975

Macromolecular characterization of muscle membranes. Endogenous membrane kinase and phosphorylated protein substrate from normal and denervated muscle.

Light density membranes derived from the "microsomal" fraction of rat skeletal muscle contained an endogenous protein kinase which catalyzed the phosphorylation of an endogenous membrane substrate. No other membrane fraction contained any significant protein kinase activity. The optimal specific activity of the enzyme in these membranes was 350 pmol/mg/min. The endogenous muscle membrane protein kinase required magnesium, was stimulated by micromolar concentrations of calcium, had a pH optimum between 7.0 and 7.5, and demonstrated a K-m for ATP of 2.6 times 10 minus 5 M. The enzyme was markedly heat labile and demonstrated a linear Arrhenius plot with an apparent energy of activation of 12,100 cal/mol. There was no stimulation by cyclic nucleotides; and neither monovalent cations nor various neurotransmitters exerted any effect. It is presently unclear where the membranes exhibiting protein phosphorylation are localized within the muscle fiber. Enzyme markers suggest that these membranes are not derived from sarcolemma or sarcoplasmic reticulum but may originate in transverse tubules. The membrane phosphorylation was largely confined to a polypeptide with an apparent molecular weight of 28,000. Phosphorylation could also be detected in a lower molecular weight substrate as well as two polypeptides with apparent molecular weights of 95,000 and 56,000. The M-r-28,000 endogenous protein kinase substrate was isolated by preparative gel electrophoresis in sodium dodecyl sulfate. High voltage electrophoresis of a partial acid hydrolysate of the phosphorylated M-r-28,000 substrate identified the phosphate bond to be that of phosphoserine. The amino acid composition of the substrate was neither strongly acidic nor basic. It had a high content of glycine, glutamic acid, serine, and lysine. Hydrophobic residues constituted only 45% of the total composition. Following muscle denervation for 10 days, there was a significant decrease in the amount of the M-r-28,000 polypeptide as well as the extent of phosphorylation.

Animals↗
PubMed1975

Characterization of neuromuscular blocking action of piperidine derivatives.

cis and trans forms of 2-methyl-6-n-undecyl piperidines (C-11) are the main constituents of fire ant venom and have been studied for their mechanism of action on the neuromuscular transmission of the nerve-sartorius muscle preparation of frogs. At low concentrations (l times 10(-6)-2 times 10(-5) M), cis- and trans-C-11 irreversibly decreased the amplitude of spontaneous miniature end-plate potentials nerve-evoked end-plate potentials and iontophoretically induced acetylcholine depolarizations without changing the membrane potential. The quantal content and the focally recorded action potentials of nerve terminals remain unchanged. It was concluded that the piperidine derivatives block neuromuscular transmission postsynaptically through a decrease in the sensitivity of the end-plate membrane to acetylcholine. Pretreatment of the end-plate with d-tubocurarine did not effect the blocking action of trans-C-11. In direct binding experiments, trans-C-11 did not compete for the sites occupied by alpha-bungarotoxin, decamethonium, carbamylcholine and d-tubocurarine. These data suggest that trans-C-11 does not bind to the acetylcholine receptor site where the other cholinergic ligands have their affinity. It appears that these piperidine derivatives interfere with the coupling mechanism between acetylcholine-receptor binding and ionic conductance increases.

Acetylcholine↗
PubMed1974

Serum globulin in myasthenia gravis: inhibition of alpha-bungarotoxin binding to acetylcholine receptors.

Serum factors that inhibit the binding of (125)I-labeled alpha-bungarotoxin to the acetylcholine receptor extracted in detergent from denervated rat muscle were detected by a sensitive assay. The serum of at least 5 and possibly 11 out of 15 patients with myasthenia gravis showed inhibitory activity that was localized to the globulin fraction. No controls showed inhibitory activity. The demonstration of inhibitory globulins may help explain the involvement of the immune system in the pathophysiology of the neuromuscular junction in patients with myasthenia gravis.

Acetylcholine↗
PubMed1973

Phosphorylation of muscle membranes: identification of a membrane-bound protein kinase.

A membrane-bound protein kinase occurs in membranes derived from rat skeletal muscle and appears limited to a surface membrane fraction. The enzyme is magnesium dependent, is only minimally stimulated by cyclic nucleotides, and phosphorylates serine and to a lesser extent threonine residues of three membrane proteins with molecular weights of less than 30,000.

Adenosine Triphosphate↗
PubMedDate not supplied

A possible role for glucocorticoids in denervation atrophy.

Skeletal muscle atrophies after denervation. Glucocorticoids also cause skeletal muscle to atrophy. The data presented in this report demonstrate that after denervation there is a significant increase in the number of glucocorticoid receptors in the cytosol of skeletal muscle of rats. The results are consistent with the hypothesis that a skeletal muscle atrophies after denervation because it becomes hypersensitive to glucocorticoids.

Animals↗