Showing papers by "Edson X. Albuquerque published in 1987"

The Molecular Basis of Anticholinesterase Actions on Nicotinic and Glutamatergic Synapsesa

Abstract: In the last 15 years, our knowledge of receptor function has been advanced considerably by studies of the acetylcholine-receptor-ion-channel complex (AChR) of the neuromuscular junction. The Occurrence of nicotinic AChRs at very high densities in Torpedo and Electrophorus electric organs made this membrane receptor easily available for study. In addition, specific chemical probes for the different active sites have contributed significantly to our understanding of the morphology and function of this receptor. In the early 19709, a-bungarotoxin (a-BGT) was isolated from snake venoms and was found to bind irreversibly and specifically to the acetylcholine (ACh) recognition site on the nicotinic AChR.’ The availability of such a highly selective probe allowed the isolation, purification, functional reconstitution into artificial lipid membranes, and, ultimately, cloning of the different subunits that comprise the nicotinic AChR.2” The pharmacological characterization of another class of toxins, the histrionicotoxins (HTX), isolated from skin secretions of frogs of the family Dendrobatidae,6*’ disclosed an important new class of sites on the nicotinic AChR. These sites, distinct from the agonist recognition site and most likely located on the ion channel component of the AChR, are responsible for allosteric alterations or noncompetitive blockade of neuromuscular transmission. Drugs with distinct and well-

Activation and Blockade of the Nicotinic and Glutamatergic Synapses by Reversible and Irreversible Cholinesterase Inhibitors

Abstract: The nicotinic acetylcholine receptor-ionic channel (AChR)4 of the neuromuscular junction, particularly that from Torpedo electric tissue, is the best characterized of all receptors. It has been functionally isolated, and the topographic arrangement of the polypeptide subunits and the amino acid composition have been detailed (Klymkowsky et al., 1980; Karlin et al., 1983; Noda et al., 1983; Sakmann et al., 1985). The involvement of some of these subunits in the binding sites for drugs has been determined biochemically and electrophysiologically (Krodel et al., 1979; Horn et al., 1980; Karlin, 1980; Aguayo et al., 1981; Spivak and Albuquerque, 1982; Changeux et al., 1984; Wan and Lindstrom, 1984).