Binding of tryptamine and 5-hydroxytryptamine (serotonin) to nucleic acids. Fluorescence and proton magnetic resonance studies

Hélène, Claude; Dimicoli, Jean‐Luc; Brun, Francine

doi:10.1021/bi00796a025

Cited by 127 publications

(25 citation statements)

References 29 publications

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“…As indicated in our autoradiographs, 3 H-/-norepinephrine not associated with tissue sites is completely washed out during the dehydration procedure; thus, radioactivity is not found indiscriminately associated with other structures in the lung. The labeling of nuclei in the presence of 3 H-/-norepinephrine is also observed with 3 H-5-hydroxytryptamine (7); this finding agrees with studies showing that 5-hydroxytryptamine can bind to the bases of nucleic acids (25,26). Whether this phenomenon is also true for norepinephrine is unknown, but it is conceivable that, if 3 H-/-norepinephrine is not firmly bound within the cytoplasm of the cell, it could become available for binding to the nucleus during perfusion fixation with glutaraldehyde.…”

Section: Discussionsupporting

confidence: 87%

Site and Mechanism of Uptake of ³ H-/-Norepinephrine by Isolated Perfused Rat Lungs

Nicholas

Strum

Angelo

et al. 1974

Circulation Research

113

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The uptake of 'H-i-norepinephrine was examined in isolated perfused rat lungs, and the mechanism of uptake was compared with that previously found for 5-hydroxytryptamine. Most of the norepinephrine taken up by the lungs was rapidly deaminated and O-methylated, and the metabolic products were subsequently returned to the perfusate. The presence of iproniazid and tropolone markedly inhibited this metabolism; because the metabolites were released from the lungs more rapidly than was norepinephrine itself, these inhibitors appeared to increase the rate of uptake of the amine. The uptake of norepinephrine was a saturable, temperature-dependent process with a K m of 1.11 x 10"'M and a Vm,, measured during metabolic inhibition of 2.78 x 10"* moles/g min" 1 . Uptake was inhibited by cocaine, imipramine, ouabain, and potassium-free medium as well as by decreasing the sodium concentration or increasing the potassium concentration of the medium. Although normetanephrine reduced the uptake of norepinephrine, metaraminol had no effect. Autoradiography indicated that norepinephrine was taken up into endothelial and smooth muscle cells, but the mechanism of the uptake appeared to combine features characteristic of both extraneuronal and neuronal uptake. The mechanism of uptake of norepinephrine by the lungs is compatible with a sodium-dependent, carrier-mediated transport, but several differences appear to exist between the transport and the site of uptake of norepinephrine and 5-hydroxytryptamine. KEY WORDS pulmonary catabolism normetanephrinesodium-coupled transport endothelial cells serotonin temperature dependence amine metabolism pulmonary autoradiography• It is now well established that the lungs of many species can take up and metabolize biogenic amines (1-4). Hughes et al. (2) have demonstrated that norepinephrine is actively taken up during one passage through the pulmonary circulation by a saturable process which can be blocked by cocaine. Similar findings have been reported by Junod (3) for 5-hydroxytryptamine; the uptake of this amine by the lungs is compatible with a sodium-dependent, carrier-mediated transport process (3) that has previously been described for norepinephrine and 5-hydroxytryptamine transport in brain (5), platelets (6), and nerve endings (7). Strum and Junod (8) have presented autoradiographic evidence indicating that the uptake of 5-hydroxytryptamine from the pulmonary circulation is into endothelial cells.

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Section: Discussionsupporting

confidence: 87%

Site and Mechanism of Uptake of ³ H-/-Norepinephrine by Isolated Perfused Rat Lungs

Nicholas

Strum

Angelo

et al. 1974

Circulation Research

113

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“…This conclusion is directly supported by data from nuclear magnetic resonance and fluorescence spectroscopy studies on the interaction of tryptamine congeners with biological macromolecules [8,91 and is in agreement with results of pharmacological SAR studies on the rat fundus muscle (see [6, lo]). Our theoretical studies showed that the result of this primary interaction would be to confer on the indole ring portion of the tryptamine cations the same reactivity characteristics that this moiety would have in the neutral species uree base) [l].…”

Section: Introductionsupporting

confidence: 82%

Models for molecular mechanisms in drug-receptor interactions. Serotonin and 5-hydroxyindole complexes with imidazolium cation

Weinstein

Osman

2009

Int. J. Quantum Chem.

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The interaction of 5-hydroxytryptamine and 5-hydroxyindole with theimidazolium cation is studied in the light of previously obtained reactivity characteristics of indolealkylamines in order to identify molecular determinants for the interaction of tryptamines with biological receptors. The complexes are calculated by a pseudopotential method. Results from this method are shown to be in excellent agreement with a6 inirio calculations on the separated molecules. At an interplanar interaction distance of 3.3 A, suggested by crystallographic studies on the complexes of serotonin, the interaction is found to be mainly electrostatic: the transfer of charge to the imidazolium cation is negligible; the mutual polarization of the molecule is the major component of the electron charge redistribution. The degree of polarization affects the stabilization energy of the complex and is dependent on the mutual orientation of the molecules. The favorable orientation coincides with the interaction geometry predicted by electrostatic reactivity criteria derived for the separated molecules. The nature and localization of the stabilizing polarization serves as a first indication of the possible electronic mechanisms involved in the triggering of a biological receptor by drugs from the tryptamine series.

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“…Since the calculations are performed on isolated molecules and solvent effects are not taken into account, it is encouraging to find that some of the theoretical results presented here are qualitatively supported by in vitro measurements of electronic char-acteristics and interaction patterns of the molecules by nuclear magnetic resonance and fluorescence spectroscopy [28,29,411 as well as by tests of biological activity [12,[31][32][33].…”

Section: Introductionmentioning

confidence: 69%

Reactivity characteristics of large molecules and their biological activity: Indolealkylamines on the LSD/serotonin receptor

Weinstein

Chou

Kang

et al. 2009

Int. J. Quantum Chem.

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Theoretical quantum mechanical methods for the characterization of molecular reactivity are applied to a series of hydroxy substituted indolealkylamines. A correlation is sought between the reactivity characteristics of these molecules and their biological activity on the LSD/serotonin receptor. The calculations are based on ab initio LCAO-SCF-MO wave functions. For the analysis of the early stages of drug-receptor interaction, the electrostatic potential fields calculated for the various congeners are compared to the field generated by the most active compound: 5-hydroxytryptamine. A model for the comparative orientation of the active molecules in the series is obtained on the basis of a requirement for matching electrostatic interaction fields. This requirement can be translated into observed differences in the affinity of the molecules for the biological receptor. The hypotheses for subsequent interactions with the receptor at shorter distances are analyzed in terms of the comparative ability of the molecules to interact in polarization-type complexes. The analysis focuses on the different localization of the most active sites in the various molecules. The largest single-orbital contribution to a polarization term E2 in a perturbation expansion of the interaction between the molecule and an attacking charge is shown to come from the highest occupied molecular orbital (HOMO). This illustrates the relation between the well established frontier density criteria for reactivity and a perturbation representation of the interaction. The localization of HOMO density is found to match the sites at which the highest percentile contribution to the polarization is calculated. These findings provide a theoretical background for previously obtained correlations between biological activity and electronic structure and answer some of the questions raised by correlations with charges on atoms and frontier densities. All the findings are in excellent qualitative agreement with the biological data on the specific binding of hydroxy substituted indolealkylamines to the LSD receptor, and with data on the pharmacological activity of these compounds.

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Binding of tryptamine and 5-hydroxytryptamine (serotonin) to nucleic acids. Fluorescence and proton magnetic resonance studies

Cited by 127 publications

References 29 publications

Site and Mechanism of Uptake of ³ H-/-Norepinephrine by Isolated Perfused Rat Lungs

Site and Mechanism of Uptake of ³ H-/-Norepinephrine by Isolated Perfused Rat Lungs

Models for molecular mechanisms in drug-receptor interactions. Serotonin and 5-hydroxyindole complexes with imidazolium cation

Reactivity characteristics of large molecules and their biological activity: Indolealkylamines on the LSD/serotonin receptor

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Binding of tryptamine and 5-hydroxytryptamine (serotonin) to nucleic acids. Fluorescence and proton magnetic resonance studies

Cited by 127 publications

References 29 publications

Site and Mechanism of Uptake of 3 H-/-Norepinephrine by Isolated Perfused Rat Lungs

Site and Mechanism of Uptake of 3 H-/-Norepinephrine by Isolated Perfused Rat Lungs

Models for molecular mechanisms in drug-receptor interactions. Serotonin and 5-hydroxyindole complexes with imidazolium cation

Reactivity characteristics of large molecules and their biological activity: Indolealkylamines on the LSD/serotonin receptor

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Site and Mechanism of Uptake of ³ H-/-Norepinephrine by Isolated Perfused Rat Lungs

Site and Mechanism of Uptake of ³ H-/-Norepinephrine by Isolated Perfused Rat Lungs