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R D O'Brien

Publications and source records attributed to R D O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1975

The charge-transfer constant. A new substituent constant for structure-activity relationships.

A new, versatile constant accounting for the pi-complex formation ability of aromatic systems is proposed. The constant is derived from charge-transfer complex data of aromatic species (charge-transfer constant, CT). The applicability of CT in structure-reactivity relations is demonstrated. It is shown that the affinity of various inhibitors (32) and acetylcholinesterase is a function of CT and pi (Hansch hydrophobicity constant).

Benzene Derivatives↗
PubMed1972

Macromolecules from lobster axon membranes that bind cholinergic ligands and local anesthetics (recpetors-procaine-acetylcholine-nicotine-Na + and K + gates).

The technique of reversible equilibrium dialysis has been applied to the study of macromolecules that are essential for axonal conduction. A binding component from a preparation of an axon-plasma membrane has been characterized and shown to bind nicotine with a K(D) = 0.42 +/- 0.04 muM and to the extent of 0.7 nmol/g of wet nerve. This binding was competitively blocked by acetylcholine (K(i) = 43 +/- 7 muM) and procaine (K(i) = 2.9 +/- 0.2 muM). This axonal macromolecule exhibits several of the properties of cholinergic postsynaptic receptors including its concentration in the tissue, blockade of its binding of nicotine by cholinergic drugs and alpha-bungarotoxin, and its phospholipoprotein nature. Some important differences are a lower affinity for acetylcholine and its binding of procaine. It is suggested that this nicotine receptor is on the internal surface of the axon plasma membrane and is a component common to both the Na(+) and K(+) gates.

Acetylcholine↗
PubMed1971

Binding sites for cholinergic ligands in a particulate fraction of Electrophorus electroplax.

The binding of four radioactive cholinergic ligands to a particulate fraction of Electrophorus electricus electroplax was investigated by equilibrium dialysis and found to be reversible. A single site (concentration, 0.02-0.03 nmol/g electroplax) that bound muscarone and nicotine was found to be on a phospholipoprotein; it is suggested that this is the acetylcholine receptor. Four binding sites for decamethonium were found; the highest-affinity site (0.03 nmol/g) may be the same one that binds muscarone and nicotine, both because of the chemical nature of the binding macromolecule and because decamethonium competes with muscarone and nicotine in binding. Dimethylcurare bound to three sites. The lower-affinity sites appeared to be on different macromolecules.When binding of the four cholinergic ligands (at 0.01 muM) to 28 arbitrarily selected proteins was determined, it was concluded that muscarone would be the most specific for the acetylcholine receptor, in that it bound to none of the 28 proteins tested; nicotine bound to one, dimethylcurare to two, and decamethonium to ten of the proteins. Nicotine or muscarone appear to be the ligands of choice in studying binding to the acetylcholine receptor; decamethonium appears to have inadequate specificity.

Acetylcholine↗
PubMed1971

Autoinhibition of acetylcholine binding to Torpedo electroplax; a possible molecular mechanism for desensitization.

Binding of [(3)H]acetylcholine (measured by equilibrium dialysis) to a particulate preparation of Torpedo electroplax exhibits autoinhibition at concentrations higher than 1 muM. It is suggested that autoinhibition results from acetylcholine binding to regulatory sites on its receptor macromolecules. This binding causes the change to a new and inactive conformation and rejection of acetylcholine bound to the larger number of active sites. The relationship to the physiological phenomenon of desensitization is discussed.

Acetylcholine↗