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PubMed · 8242839

Liposomes: the Babraham connection.

Abstract

A chronological history is given of the experimental work carried out at The Institute of Animal Physiology, Babraham, Near Cambridge (UK) prior to and after the first description of liposomes in 1965. A convergence of worldwide interest in membrane structure and function coupled with the coexistence of physiologists, biochemists and electron microscopists provided a unique opportunity for the development of a useful model system. As well as defining their properties, such as composition, dimensions, perm-selectivity, permeating pathways and response to solutes (oil and/or water soluble), temperature and pressure, attention is drawn to a number of ideas investigated over the years relating to in vivo 'invisibility' of foreign particles, the trapping of ions in small vesicles the origins of life, to the mechanisms of anaesthesia and formulation of an effective lung surfactant.

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BibTeXRIS

A D Bangham. 1993. Liposomes: the Babraham connection.. https://doi.org/10.1016/0009-3084(93)90071-a

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Identification of a molecular target mediating the general anesthetic actions of pentobarbital.

Barbiturates were introduced into medical practice in 1934. They are widely used today as general anesthetics. Although in vitro studies revealed that the activity of a variety of ligand-gated channels is modulated by barbiturates, the target(s) mediating the anesthetic actions of barbiturates in vivo are unknown. Studying pentobarbital action in beta3(N265M) mice harboring beta3-containing GABAA receptors insensitive to a variety of general anesthetic agents, we found that the immobilizing action of pentobarbital is mediated fully, and the hypnotic action is mediated in part by this receptor subtype. It was surprising that the respiratory depressant action of pentobarbital is indistinguishable between beta3(N265M) and wild-type mice and thus is mediated by other as-yet-unidentified targets. Whereas the target for the immobilizing and hypnotic actions of pentobarbital seems to be the same as for etomidate and propofol, these latter agents' respiratory depressant actions are mediated by beta3-containing GABAA receptors. Thus, in contrast to etomidate and propofol, pentobarbital can elicit respiratory depression by a beta3-independent pathway. Pentobarbital reduced heart rate and body temperature to a slightly smaller extent in beta3(N265M) mice compared with wild-type mice, indicating that these actions are largely mediated by other targets. Pentobarbital-induced increase of heart rate variability and prolongation of ECG intervals are seen in both beta3(N265M) mice and wild-type mice, suggesting that they are not dependent on beta3-containing GABAA receptors. In summary, we show a clear pharmacological dissociation of the immobilizing/hypnotic and respiratory/cardiovascular actions of pentobarbital.

Anesthetics↗