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W R Lieb

Publications and source records attributed to W R Lieb.

77 records · Page 5Linked to original sources
PubMed1967

Cation movements in the high sodium erythrocyte of the cat.

The uptake of (42)K and (24)Na by cat erythrocytes was investigated. Under steady-state conditions, the nontransient component of (42)K influx was found to be 0.18 +/- 0.01 meq/liter RBC/hr and insensitive to ouabain (100 microM); the corresponding value for (24)Na was 17 +/- meq/liter RBC/hr. A study was made of the effects of anions upon cation movements in these and other mammalian red cells. Iodide was found to inhibit markedly (>50%) Na inward movements in cat and dog but not in the other erythrocytes. An increase (15-30%) in K uptake in the presence of iodide was noted in all the mammalian cells studied.

Animals↗
PubMedDate not supplied

Do general anaesthetics act by competitive binding to specific receptors?

Most proteins are insensitive to the presence of anaesthetics at concentrations which induce general anaesthesia, while some are inhibited by certain agents but not others. Here we show that, over a 100,000-fold range of potencies, the activity of a pure soluble protein (firefly luciferase) can be inhibited by 50% at anaesthetic concentrations which are essentially identical to those which anaesthetize animals. This identity holds for inhalational agents (such as halothane, methoxyflurane and chloroform), aliphatic and aromatic alcohols, ketones, ethers and alkanes. This finding is all the more striking in view of the fact that the inhibition is shown to be competitive in nature, with anaesthetic molecules competing with substrate (luciferin) molecules for binding to the protein. We show that the anaesthetic-binding site can accommodate only one large, but more than one small, anaesthetic molecule. The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors.

Anesthesia, General↗
PubMedDate not supplied

Mapping of general anaesthetic target sites provides a molecular basis for cutoff effects.

A longstanding and unresolved problem in general anaesthesia is the so-called 'cutoff' effect; as one ascends a homologous series of anaesthetic agents, the potencies progressively increase with anaesthetic size but then, rather suddenly, anaesthetic potency disappears. Curiously, this cutoff in potency occurs at very different points in different series. Various explanations have been offered, usually based on the notion that lipid bilayers are the primary target sites in general anaesthesia. However, accumulating evidence now suggests that proteins are the primary sites of action. Here we demonstrate cutoff effects for the anaesthetic inhibition of a soluble protein (firefly luciferase) which mirror those found for general anaesthesia, and we describe how the molecular architecture of the binding site accounts for the different cutoffs in the different homologous series. We show that this behaviour is a natural consequence of anaesthetics binding to an amphiphilic protein pocket of circumscribed dimensions. When general anaesthetic target sites in animals and the luciferase protein are mapped out using the fine details of the potency data, remarkable similarities are revealed. Our results thus suggest that the target sites in general anaesthesia are amphiphilic pockets on proteins.

Alcohols↗