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Biomedical subjects

B Witkop

Publications and source records attributed to B Witkop.

At least 73 records · Page 4Linked to original sources
PubMed1973

Acetylcholine receptor and ion conductance modulator sites at the murine neuromuscular junction: evidence from specific toxin reactions.

The perhydro derivative of histrionicotoxin reversibly blocks the excitatory ionic transduction system in the synaptic and sarcolemmal membranes of mammalian skeletal muscle cells. The efficacy of perhydrohistrionicotoxin as an antagonist at the post-synaptic membrane is increased by the transient presence of acetylcholine in the endplate of innervated muscles and at extrajunctional receptors in denervated muscles. alpha-Bungarotoxin and [(3)H]monoacetyl-alpha-bungarotoxin block the endplate acetylcholine receptors, each binding to the same extent. The effect of bungarotoxin is partially reversible. These electrophysiological results, together with the effects of perhydrohistrionicotoxin and/or d-tubocurarine on the binding of [(3)H]monoacetyl-alpha-bungarotoxin at endplates of murine diaphragm muscle and on the bungarotoxin-elicited irreversible blockade of neuromuscular transmission, suggest that at least two types of sites participate in the synaptic excitation by acetylcholine. One site, competitively blocked by bungarotoxin and by curare, is presumably the acetylcholine receptor. Binding of bungarotoxin at this site is responsible for an irreversible blockade of neuromuscular transmission. The second site, competitively blocked by bungarotoxin and perhydrohistrionicotoxin, is proposed to be part of the cholinergic ion conductance modulator. Binding of bungarotoxin to this site does not result in an irreversible blockade.

Acetylcholine↗
PubMed1973

Conformations of the li-antamanide complex and na-[phe, val]antamanide complex in the crystalline state.

Antamanide, a cyclic decapeptide isolated from the poisonous mushroom Amanita phalloides, preferably complexes with Na(+), but in less polar solvents, e.g., acetonitrile, also with Li(+) or K(+). The selectivity of complexation makes it an important model for the study of conformational requirements of ion binding. The conformations of the lithium antamanide complex and the Na-[Phe(4), Val(6)]antamanide complex have been established by x-ray diffraction analyses of single crystals. The two compounds are isostructural, but not isomorphous. The complexes are folded into a globular shape with an approximate 2-fold axis. Two of the peptide linkages are in the cis conformation, Pro(2)-Pro(3) and Pro(7)-Pro(8). There are only two intramolecular hydrogen bonds. Four C==O groups have their O atoms directed inward to form four Li-O or Na-O ligands. The fifth ligand to the metal ion is provided by a solvent molecule. The conformation found in the crystalline state is different from any of the conformations proposed for the sodium antamanide complex in solution on the basis of nuclear magnetic resonance data.

Journal Article↗
PubMed1971

Batrachotoxin: chemistry and pharmacology.

Batrachotoxin has been shown to be a pyrrolecarboxylic ester of a novel steroidal base with unique and selective actions on a variety of electrogenic membranes. The effects of batrachotoxin in neuromuscular preparations both pre- and postsynaptically, in nerve axons, in superior cervical ganglion, in heart Purkinje fibers, and in brain slices appear to be due to the selective and irreversible increase in permeability of membranes to sodium ions. The subsequent effects of this increase in Na(+) permeability evoked by batrachotoxin-such as membrane depolarization, enhanced spontaneous transmitter release, muscle contracture, and enhanced formation of cyclic AMP in brain slices-may be blocked reversibly by tetrodotoxin.

Acetylcholine↗