Cation Permeability of Phospholipid Model Membranes: Effect of Narcotics

Bangham, A. D.; Standish, M. M.; Miller, Nigel

doi:10.1038/2081295a0

Cited by 194 publications

(51 citation statements)

References 10 publications

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“…Anisotropy was derived from P using R ϭ 2P/(3 Ϫ P). Similar measurements were performed on POPC and DPPC multilamellar liposomes prepared as described by Bangham et al (1965).…”

Section: Methodsmentioning

confidence: 77%

Modulation by LL-37 of the Responses of Salivary Glands to Purinergic Agonists

Pochet

Tandel²,

Querriére³

et al. 2006

Mol Pharmacol

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The interaction of mice submandibular gland cells with LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), a cationic peptide with immunomodulatory properties, was investigated. LL-37 at a concentration that did not affect the integrity of the cells increased the uptake of calcium and activated a calciuminsensitive phospholipase A 2 (PLA 2 ). The small release of ATP induced by LL-37 could not account for this stimulation because apyrase did not significantly block the response to LL-37. The divalent cation magnesium inhibited the response to LL-37, but this inhibition was probably nonspecific because it also inhibited the in vitro bacteriostatic effect of the peptide. The increase of calcium uptake by LL-37 was not affected by, a rather specific inhibitor of P2X 7 receptors in mice. LL-37 also increased [Ca 2ϩ ] i in cells from mice invalidated for these receptors. LL-37 had no effect on the response to carbachol. It inhibited the increase of [Ca 2ϩ ] i and the activation of phospholipase D by ATP. It potentiated the activation of the PLA 2 by the nucleotide. Finally, LL-37 increased the fluidity of the plasma membrane of submandibular gland cells. In conclusion, our results suggest that LL-37 is an autocrine regulator of submandibular gland cells. It does not stimulate mouse P2X 7 receptors but modulates their responses.Cathelicidins are proteins involved in the first phases of our defenses against pathogens. Their isolation relied on the analogy of their N-terminal proregions with cathelin, an inhibitor of cathepsin L originally isolated from bovine leukocytes (Ritonja et al., 1989). This highly conserved proregion (approximately 100 amino acids) shares many similarities with cystatins, inhibitors of the cysteine proteases. The Cterminal domain of cathelicidins varies among species both in terms of length (12-100 amino acids) and structure. The N-and C-terminal domains are separated by a sequence recognized by proteases. The digestion in the extracellular medium of the propeptides by elastase (Panyutich et al., 1997) or proteinase 3 (Sorensen et al., 2001) releases the C-terminal peptides originally described as antimicrobial but that now prove to be more immunomodulatory than antimicrobial in physiological conditions (Bowdish et al., 2005). Most of the studies on cathelicidins have focused on the C-terminal peptides. These peptides are ubiquitous. They are secreted by macrophages, lymphocytes, epithelial cells, keratinocytes, cells lining the upper respiratory tree, and vaginal cells (Bals and Wilson, 2003). LL-37, the only peptide from human origin, is derived from an antibacterial protein of 18 kDa. LL-37 and its only analog in mouse, the cathelinrelated antimicrobial peptide, are cationic and transform from a random coil in aqueous solution to an amphipathic ␣-helix at the contact of a membrane (Yeaman and Yount, 2003). The peptide binds to the bacteria by electrostatic interactions between the positive charges on one side of its

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“…Anisotropy was derived from P using R ϭ 2P/(3 Ϫ P). Similar measurements were performed on POPC and DPPC multilamellar liposomes prepared as described by Bangham et al (1965).…”

Section: Methodsmentioning

confidence: 77%

Modulation by LL-37 of the Responses of Salivary Glands to Purinergic Agonists

Pochet

Tandel²,

Querriére³

et al. 2006

Mol Pharmacol

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“…This work demonstrates clearly, for the first time, that GA3 can influence the permeability of model membranes, composed of plant constituents, which have many characteristics in common with their more complex and sophisticated natural counterparts (2,3). The alterations in permeability demonstrated are not mediated by enzymes, do not involve carrier systems, and do not depend on the presence of charges on the permeating molecules.…”

Section: Discussionmentioning

confidence: 93%

The Influence of Gibberellic Acid on the Permeability of Model Membrane Systems

Wood

Paleg

1972

Plant Physiol.

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Gibberellic acid increases the permeability of model membranes composed of various plant-source lipids, a sterol, and dicetyl phosphate. As a result of hormone treatment, the flux of uncharged molecules such as glucose or sucrose, or charged ions such as chromate, through the model membranes (liposomes or micelies) is increased. The revelance of this finding to the in vivo effects of the hormone is briefly discussed.Plant hormones are both fewer in number and less variable in structure and function than their animal counterparts. In only one case, the gibberellins, do plant hormones approach the diversity apparent with animal steroids. These two classes of compounds, steroids and gibberellins, also share the properties of isoprenoid structure (and, thus, a common biosynthetic pathway), similarity in structural diversity (through insertion or deletion of double bonds, radicals, subsidiary ring structures), and control of comparable physiological functions. It would seem possible that gibberellins and steroids also share at least one common trigger or hormonal mechanism.One of the simplest manifestations of steroid action is the alteration of permeability of synthetic model membrane systems (3,9,21). The models are based on the fact that phospholipids, one of the major components of natural membranes, when dispersed in aqueous media, produce self-ordered particles which display many of the properties of natural membranes (6). The physiological pertinence of the models was enhanced by the finding that they demonstrated comparable responses to compounds which affect membranes in vivo (3). The permeability of the model structures (micelles or liposomes) is influenced by detergents, some antibiotics, and toxins, which increase permeability, and anti-inflammatory drugs and anaesthetics, which decrease permeability (16). Sterols may either increase or decrease permeability of the liposomes, and in one study, there was a high degree of correlation between the release of acid phosphatase from lysosomes and the increase in permeability of liposomes, with a range of sterols (3). Some sterols which decrease permeability of the model system have also been shown to act in a similar way in higher plant tissue, i.e., they protect red beet tissue from alcohol-induced damage in vivo (8). In addition, the in vivo effect of the polyene antibiotic, filipin, in increasing permeability of pea stem tissue, red beet, and potato discs (12,17), closely parallels its effect on liposomes. Furthermore, the effects of filipin, in both the in vivo and the in vitro systems, can be overcome by cholesterol (12).An explanation of hormone action in terms of alterations in membrane permeability has been a perennially proposed possibility. In general, the concept has met with only very limited success, for several reasons, and most workers continue to concentrate on more "metabolic explanations." In this and succeeding papers the potential role of gibberellin as a regulator of membrane permeability will be explored. MATERIALS AND METHODSTo pre...

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“…The use of extracted phospholipids to reconstitute cell membranes was achieved by Bangham in 1965(Bangham et al 1965a) and the term liposome was coined. Summarizing several observations from in vivo to in vitro studies, Singer and Nicolson determined that cell membranes were highly fluid and homogeneous and established the fluid mosaic model in 1972 (Singer and Nicolson 1972), where proteins are rapidly diffusing in a "sea" of lipids.…”

Section: Evolution Of Understanding Of Lipid Membranesmentioning

confidence: 99%