NMR studies of 5-hydroxytryptamine transport through large unilamellar vesicle membranes.

Viscio, David B.; Prestegard, James H.

doi:10.1073/pnas.78.3.1638

Cited by 8 publications

(10 citation statements)

References 11 publications

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“…Unfortunately, image intensities do not yield a reliable absolute measurement because of the large uncertainty of fluorescence quantum yield and spectral characteristics of serotonin inside the unknown and possibly complex environment of the vesicles (Nag et al, 2008). For example, serotonin possibly makes a complex with ATP inside the vesicles (Viscio and Prestegard, 1981). Multiphoton excitation can also create transient photoproducts of serotonin with very different fluorescence properties, and the population of these photoproducts may depend on the degree of confinement of the chemical species (Gostkowski et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Three‐photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brain

Kaushalya

Desai

Arumugam

et al. 2008

J of Neuroscience Research

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Recent experiments on monoaminergic neurons have shown that neurotransmission can originate from somatic release. However, little is known about the quantity of monoamine available to be released through this extrasynaptic pathway or about the intracellular dynamics that mediate such release. Using three-photon microscopy, we directly imaged serotonin autofluorescence and investigated the total serotonin content, release competence, and release kinetics of somatic serotonergic vesicles in the dorsal raphe neurons of the rat. We found that the somata of primary cultured neurons contain a large number of serotonin-filled vesicles arranged in a perinuclear fashion. A similar distribution is also observed in fresh tissue slice preparations obtained from the rat dorsal raphe. We estimate that the soma of a cultured neuron on an average contains about 9 fmoles of serotonin in about 450 vesicles (or vesicle clusters) of < or =370 nm average diameter. A substantial fraction (>30%) of this serotonin is released with a time scale of several minutes by K(+)-induced depolarization or by para-chloroamphetamine treatment. The amount of releasable serotonin stored in the somatic vesicles is comparable to the total serotonin content of all the synaptic vesicles in a raphe neuron, indicating that somatic release can potentially play a major role in serotonergic neurotransmission in the mammalian brain.

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Section: Discussionmentioning

confidence: 99%

Three‐photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brain

Kaushalya

Desai

Arumugam

et al. 2008

J of Neuroscience Research

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“…There is considerable experimental evidence that the indole moiety of serotonin can also participate in stacking interactions (9,10). The stacking of serotonin and ATP molecules is also well documented (11)(12)(13). These results suggest that intravesicular serotonin may not exist in a purely monomeric state.…”

Section: Introductionmentioning

confidence: 93%

Intermolecular Association Provides Specific Optical and NMR Signatures for Serotonin at Intravesicular Concentrations

Nag

Balaji

Madhu

et al. 2008

Biophysical Journal

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Neurotransmitter vesicles contain biomolecules at extraordinarily high concentrations (hundreds of millimoles/liter). Such concentrations can drive intermolecular associations, which may affect vesicular osmolarity and neuronal signaling. Here we investigate whether aqueous serotonin (a monoamine neurotransmitter) forms oligomers at intravesicular concentrations and whether these oligomers have specific spectroscopic signatures that can potentially be used for monitoring neuronal storage and release. We report that, as serotonin concentration is increased from 60 microM to 600 mM, the normalized fluorescence spectrum of serotonin displays a growing long-wavelength tail, with an isoemissive point at 376 nm. The fluorescence decay is monoexponential with a lifetime of 4 ns at low concentrations but is multiexponential with an average lifetime of 0.41 ns at 600 mM. A 600 mM serotonin solution has 30% less osmolarity than expected for monomeric serotonin, indicating oligomer formation. The proton NMR chemical shifts move upfield by as much as 0.3 ppm at 600 mM compared to those at 10 mM, indicating a stacking of the serotonin indole moieties. However, no intermolecular crosspeak is evident in the two-dimensional NMR rotating frame Overhauser effect spectroscopy spectrum even at 600 mM, suggesting that oligomeric structures are possibly weakly coupled. The appearance of a single peak for each proton suggests that the rate of interconversion between the monomeric and the oligomeric structures is faster than 240 Hz. A stopped-flow kinetic experiment also confirms that the rate of dissociation is faster than 100 ms. We conclude that serotonin forms oligomers at intravesicular concentrations but becomes monomeric quickly on dilution. NMR signatures of the oligomers provide potential contrast agents for monitoring the activity of serotonergic neurons in vivo.

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“…At circumneutral pH, the apparent permeation coefficient of glyphosate (double negatively charged, molecular weight (MW) = 167 g•mol −1 ) P app (pH 7.0) = 3.7 (±0.3) × 10 −7 m• s −1 was considerably higher than that of maleate 46 (net dianion, MW = 114 g•mol −1 ) and in the same range as the permeation coefficient of the polar, neutral serotonin species (MW = 176 g• mol −1 ). 58 With decreasing pH, the permeation rate increased, with an apparent permeation coefficient of P app (pH 4.1) = 4.2 (±0.1) × 10 −6 m•s −1 at pH 4.1. The pH dependence correlated linearly with the average degree of ionization and thus the average charge of glyphosate (Figure 3B).…”

Section: Environmental Science and Technologymentioning

confidence: 99%

“…At circumneutral pH the apparent permeation coefficient of glyphosate (double negatively charged, molecular weight MW = 167 g•mol -1 ) Papp(pH 7.0) = 3.7 ( 0.3) × 10 -7 m•s -1 was considerably higher than the one of maleate 46 (double negatively charged, MW = 114 g•mol -1 ) and in the same range as the permeation coefficient of the polar, neutral serotonin species (MW = 176 g•mol -1 ). 58 With decreasing pH, the permeation rate increased, with an apparent permeation coefficient of (3)…”

Section: Abstract Art Introductionmentioning

confidence: 99%

“…60,61 Contrary to this expectation, our observations in a liposome model system that lacked transporters or porins gave membrane permeation coefficients of glyphosate in the same range as those of non-charged molecules (see above). 58 This observation suggests that passive membrane permeation of glyphosate mono-and dianions may provide sufficient influx into bacterial cells for it to serve as phosphorus source. Because the diffusion through water of glyphosate is fast compared with the diffusion through the lipid membrane, 62,63 , the membrane as significant barrier influences how fast the molar amount of substrate outside the bacteria nout is reduced via passive membrane permeation at the rate (dnout/dt)permeation.…”

Section: Abstract Art Introductionmentioning

confidence: 99%

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High Permeation Rates in Liposome Systems Explain Rapid Glyphosate Biodegradation Associated with Strong Isotope Fractionation

Ehrl

Mogusu

Kim

et al. 2018

Environ. Sci. Technol.

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Bacterial uptake of charged organic pollutants such as the widely used herbicide glyphosate is typically attributed to active transporters, whereas passive membrane permeation as an uptake pathway is usually neglected. For 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine (POPC) liposomes, the pH-dependent apparent membrane permeation coefficients ( P) of glyphosate, determined by nuclear magnetic resonance (NMR) spectroscopy, varied from P (pH 7.0) = 3.7 (±0.3) × 10 m·s to P (pH 4.1) = 4.2 (±0.1) × 10 m·s. The magnitude of this surprisingly rapid membrane permeation depended on glyphosate speciation and was, at circumneutral pH, in the range of polar, noncharged molecules. These findings point to passive membrane permeation as a potential uptake pathway during glyphosate biodegradation. To test this hypothesis, a Gram-negative glyphosate degrader, Ochrobactrum sp. FrEM, was isolated from glyphosate-treated soil and glyphosate permeation rates inferred from the liposome model system were compared to bacterial degradation rates. Estimated maximum permeation rates were, indeed, 2 orders of magnitude higher than degradation rates of glyphosate. In addition, biodegradation of millimolar glyphosate concentrations gave rise to pronounced carbon isotope fractionation with an apparent kinetic isotope effect, AKIE, of 1.014 ± 0.003. This value lies in the range typical of non-masked enzymatic isotope fractionation demonstrating that glyphosate biodegradation was not subject to mass transfer limitations and glyphosate exchange across the cell membrane was rapid relative to enzymatic turnover.

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NMR studies of 5-hydroxytryptamine transport through large unilamellar vesicle membranes.

Cited by 8 publications

References 11 publications

Three‐photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brain

Three‐photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brain

Intermolecular Association Provides Specific Optical and NMR Signatures for Serotonin at Intravesicular Concentrations

High Permeation Rates in Liposome Systems Explain Rapid Glyphosate Biodegradation Associated with Strong Isotope Fractionation

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