Binding of specific ligands to muscarinic receptors alters the fluidity of membrane fragments from rat brain A fluorescence polarization study with lipid‐specific probes

Manevich, E.M.; Kõiv, Anu; Järv, Jaak; Molotkovsky, Julian G.; Bergel'son, L. D.

doi:10.1016/0014-5793(88)80282-5

Cited by 16 publications

(6 citation statements)

References 11 publications

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“…In the same manner fluidity changes of the lipid environment were detected after addition of specific muscarinic ligands to rat brain membrane fragments (Fig. 3) [12] prelabeled with APC. In these experiments the muscarinic agonist, carbachol, and the antagonist, atropine, appeared to compete for the same receptor; however, the maximal effect of atropine was considerably smaller.…”

Section: R B Molecules/cellssupporting

confidence: 56%

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Lipid domain reorganization and receptor events Results obtained with new fluorescent lipid probes

Bergel'son¹

1992

FEBS Letters

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Binding of a ligand to the extracellular site of a membrane receptor involves conformational changes not only of the extracellular and cytoplasmic sites but also of the membrane-spanning segments of the receptor protein. The lipids forming the environment of the trans-membrane receptor segments, being flexible and mobile, must follow the shape changes of the receptor molecule to some extent. For this reason ligandreceptor binding itself can be expected to result in changes of the packing of lipid molecules surrounding the receptor. Since lipids are organized in a cooperative manner such changes may affect large areas of the membrane and hence can be registered by physical methods. It has been stated repeatedly that binding of various ligands including hormones, antibodies or lectins to membrane-associated receptors is accompanied by fluidity changes of the target membrane [1][2][3].The aim of this article is to summarize recent evidence suggesting that in highly heterogeneous biological membranes containing numerous metastable lipid domains and/or clusters conformational changes of membrane-associated proteins may result not only in global fluidity changes but also in alterations of the supramolecular lipid domain organization. Frequently such changes can be tbllowed by using, as fluorescent probe, analogs of natural membrane phospholipids or glycolipids bearing, at the end of one of the fatty acyl chains, a 9.anthrylvinyl (AV) group ( cells, and in the latter case may reside for a relatively long time in the plasma membrane without internalization [7].In comparison to most other fluorophores used in membrane research, the AV group displays important advantages. It causes little disturbance because it is nonpolar, flat, and relatively compact. When attached to the fatty acyl chain at an appropriate distance from the head group the AV-fluorophores reside uniformly and exclusively in the center of the bilayer where the host lipids are packed most loosely, and affect neither the mobility nor the orientation and conformation of the major part of the molecules of the surrounding host lipids including their head groups [8]. The AV-group is characterized also by high quantum yields and very short fluorescence lifetimes [9]. The latter property makes the AV-fluorophore suitable for fluorescence polarization measurements. Moreover, in phospholipid bilayers the restricted rotational diffusion of the AVlabeled lipid molecules is of the same time scale as the fluorescence decay. Therefore even subtle changes in the fluidity of the probes microenvironment produce considerable changes in the polarization of fluorescence. The fluorescent parameters of the AV-group (,~ 365 nm, A,~m 430 rim; high extinction coefficient) make it also a highly efficient acceptor for resonance energy transfer (RET) from nearby tryptophans. Since the distance that RET can occur over is as long as 5 nm while RET efficiency depends on the sixth power of the donoracceptor distance, RET measurements with AV-labeled lipids permits the following of even e...

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Section: R B Molecules/cellssupporting

confidence: 56%

“…3) [12] prelabeled with APC. In these experiments the muscarinic agonist, carbachol, and the antagonist, atropine, appeared to compete for the same receptor; however, the maximal effect of atropine was considerably smaller.…”

Section: R B Molecules/cellsmentioning

confidence: 99%

Lipid domain reorganization and receptor events Results obtained with new fluorescent lipid probes

Bergel'son¹

1992

FEBS Letters

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“…Supporting Figure S7 shows that NOE(−3.5) may arise from both proteins and methylene protons of membrane phospholipids, while NOE(−1.6) may arise from the phospholipid choline head groups that have a resonance frequency at around −1.6 ppm. The NOE(−1.6) coupling rate may depend on the choline head group mobility, which may be regulated by the phospholipid head group conformation and charge, membrane component, and insertion of small amphiphilic molecules into lipid bilayers . The NOE(−1.6) effect may also be relayed between successive protons through multiple‐step spin diffusion.…”

Section: Discussionmentioning

confidence: 99%

“…The NOE(−1.6) coupling rate may depend on the choline head group mobility, which may be regulated by the phospholipid head group conformation and charge, 66,67 membrane component, and insertion of small amphiphilic molecules into lipid bilayers. [68][69][70][71][72][73] The NOE(−1.6) effect may also be relayed between successive protons through multiple-step spin diffusion. A further evaluation of the mechanism for the variation of the NOE(−1.6) coupling rate in tumors is warranted, because it may represent a new biomarker of pathologies and physiologies.…”

Section: Discussionmentioning

confidence: 99%

Ratiometric NOE(−1.6) contrast in brain tumors

2018

NMR in Biomedicine

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Recently, a new nuclear Overhauser enhancement (NOE)‐mediated saturation transfer effect at around −1.6 ppm from water, termed NOE(−1.6), was reported to show hypointense signals in brain tumors. Similar to chemical exchange saturation transfer or magnetization transfer (MT) effects, which depend on the solute pool concentration, the exchange/coupling rate, the solute transverse relaxation rate, etc., the NOE(−1.6) effect should also depend on these factors. Since the exchange rate is relevant to tissue pH, and the coupling rate and the solute transverse relaxation rate are relevant to the motional property of the coupled molecules, further studies to quantify the contribution from only the exchange/coupling rate and the solute transverse relaxation rate are always interesting. The purpose of this paper is to apply a ratiometric approach to the NOE(−1.6) effect to obtain a metric that is more specific to the NOE coupling rate and the solute transverse relaxation rate than the NOE(−1.6) signal amplitude. Simulations indicate that the ratiometric approach allows us to rule out nearly all of the non‐specific factors including the solute pool concentration, solute and water longitudinal relaxation rates, direct water saturation, and semi‐solid MT effects, and provides a more specific NOE coupling rate‐ and solute transverse relaxation rate‐weighted signal. Animal studies show that the ratiometric NOE(−1.6) decreases dramatically in brain tumors, which suggests that the change in the NOE(−1.6) coupling rate and/or the solute transverse relaxation rate are major contributors to the previously observed hypointense NOE(−1.6) signal in tumors.

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“…For example, ethanol specifically and selectively affects the function of the GABA-coupled chloride channel [54,55]. Still, a large, diverse collection of physiological agonists produces the alterations in membrane fluidity as well as specific ligand-receptor interaction [56]. Hence the function of membrane proteins may be modulated secondarily to changes in membrane fluidity.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Methanol on the Structural Parameters of Neuronal Membrane Lipid Bilayers

Joo

Ahn

Lee

et al. 2012

Korean J Physiol Pharmacol

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The structures of the intact synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortexs, and the outer and the inner monolayer separately, were evaluated with 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) as fluorescent reporters and trinitrophenyl groups as quenching agents. The methanol increased bulk rotational and lateral mobilities of SPMVs lipid bilayers. The methanol increased the rotational and lateral mobilities of the outer monolayers more than of the inner monolayers. n-(9-Anthroyloxy)stearic acid (n-AS) were used to evaluate the effect of the methanol on the rotational mobility at the 16, 12, 9, 6, and 2 position of aliphatic chains present in phospholipids of the SPMVs outer monolayers. The methanol decreased the anisotropy of the 16-(9-anthroyloxy)palmitic acid (16-AP), 12-(9-anthroyloxy)stearic acid (12-AS), 9-(9-anthroyloxy)stearic acid (9-AS), and 6-(9-anthroyloxy)stearic acid (6-AS) in the SPMVs outer monolayer but it increased the anisotropy of 2-(9-anthroyloxy)stearic acid (2-AS) in the monolayers. The magnitude of the increased rotational mobility by the methanol was in the order at the position of 16, 12, 9, and 6 of aliphatic chains in phospholipids of the outer monolayers. Furthermore, the methanol increased annular lipid fluidity and also caused membrane proteins to cluster. The important finding is that was far greater increase by methanol in annular lipid fluidity than increase in lateral and rotational mobilities by the methanol. Methanol alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that methanol, in additions to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membranes lipids.

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Binding of specific ligands to muscarinic receptors alters the fluidity of membrane fragments from rat brain A fluorescence polarization study with lipid‐specific probes

Cited by 16 publications

References 11 publications

Lipid domain reorganization and receptor events Results obtained with new fluorescent lipid probes

Lipid domain reorganization and receptor events Results obtained with new fluorescent lipid probes

Ratiometric NOE(−1.6) contrast in brain tumors

The Effect of Methanol on the Structural Parameters of Neuronal Membrane Lipid Bilayers

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