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Biomedical subjects

R E Gibson

Publications and source records attributed to R E Gibson.

83 records · Page 5Linked to original sources
PubMed1976

Ligand interactions with the acetylcholine receptor from Torpedo californica. Extensions of the allosteric model for cooperativity to half-of-site activity.

The solubilized acetylcholine receptor from Torpedo californica showed positive cooperativity in acetylcholine binding with a dissociation constant of 1.2 X 10(-8) M. Blockade of acetylcholine binding by nicotine was competitive; blockade by d-tubocurarine appeared to result from an allosteric interaction that altered half of the acetylcholine binding sites to a lower affinity form; decamethonium blockade displayed properties of competitive and allosteric inhibition suggesting less specificity for decamethonium binding than seen with either nicotine or d-tubocurarine. The d-tubocurarine inhibition data were evaluated by several possible models involving either differential competitive inhibition or allosteric inhibiton. The data were best described by the allosteric model.

Acetylcholine↗
PubMed1976

Acetylcholine receptor oligomers from electroplax of Torpedo species.

Sedimentation in sucrose gradients of alpha-bungarotoxin-labeled crude and pure acetycholine receptor preparations from Torpedo californica showed two major oligomers. The molecular weights, corrected for the bound Triton X-100 by comparing sedimentation in H2O and in D2O, were 330 000 for the heavy (H) oligomer and 190 000 for the light (L) oligomer. Lesser peaks found in preparations of T. marmorata and purified preparations of T. californica with molecular weights of 500 000 (HH) and 80 000 (LL). These molecular weights are based upon the assumption of globularity, and may require adjustment if the assumption is wrong. The H and L peaks have similar drug sensitivities, but at pH 10 the L peak was stable whereas the H peak dissociated to components sedimenting as LL. Treatments with p-chloromercuribenzoate, which blocks acetylcholine binding partially without affecting alpha-bungarotoxin binding, had no effect upon the pattern of sedimentation. This and other evidence suggested that the heterogeneity of oligomers was unrelated to the heterogeneity of site affinities for acetylcholine and nicotinic drugs.

Acetylcholine↗
PubMed1975

A radioprotective stereostructure-activity study of cis- and trans-2-mercaptocyclobutylamine analogs and homologs of 2-mercaptoethylamine.

For purposes of studying stereostructure-activity relationships at the molecular, cellular, and animal levels and probing the mechanism of 2-mercaptoethylamine (MEA) radioprotection we synthesized several conformationally constrained cyclobutyl analogs. The comparative radioprotective properties for MEA, cis- and trans-2-mercaptocyclobutylamine (2), cis- and trans-2-mercaptocyclobutylmethylamine (3), and trans-2-mercaptomethylcyclobutylamine (4) are discussed in terms of their ability to chemically reduce transient free radicals, the formation of single strand breaks in DNA, and protect Chinese hamster cells (in vitro) and mice against the lethal effects of ionizing radiation. The results are interpreted in light of current proposed mechanisms of action for MEA. No correlation exists between ability of these analogs to enhance mice survival times and their ability to protect against the induction of DNA single strand breaks and the inactivation of proliferative capacity of hamster cells growing in vitro. Analysis of two isomers (cis- and trans-3) on the repair of single strand breaks showed both isomers only marginally influenced the rate and did not influence of extent of single strand break rejoining. The results are consistent with a mode of action involving chemical repair of transient radicals and protection against DNA and critical enzymatic sites.

Animals↗