Adrenochrome-thiol addition products

Powell, William S.; Heacock, R. A.

doi:10.1007/bf01935706

Cited by 9 publications

(2 citation statements)

References 8 publications

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“…Briefly, the primary function of GSH is to recycle oxidized ascorbic acid (dehydroascorbic acid or DHA) back into reduced ascorbic acid (ASC), thereby mediating cellular oxidative stress [136]. GSH also recycles epinephrine, norepinephrine, dopamine, and related adrenergic amines, which oxidize to form toxic adrenochrome-like compounds or forms adducts with them that are then excreted [137][138][139][140][141][142][143][144][145]. Similarly, opioids such as morphine and the enkephalins bind to GSH antagonizing its antioxidant function and forming inactive adducts [146][147][148][149][150][151].…”

Section: Evolutionary Models Of Resultsmentioning

confidence: 99%

Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

Root‐Bernstein¹,

Churchill²

2021

Life

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Cross-talk between opioid and adrenergic receptors is well-characterized and involves second messenger systems, the formation of receptor heterodimers, and the presence of extracellular allosteric binding regions for the complementary ligand; however, the evolutionary origins of these interactions have not been investigated. We propose that opioid and adrenergic ligands and receptors co-evolved from a common set of modular precursors so that they share binding functions. We demonstrate the plausibility of this hypothesis through a review of experimental evidence for molecularly complementary modules and report unexpected homologies between the two receptor types. Briefly, opioids form homodimers also bind adrenergic compounds; opioids bind to conserved extracellular regions of adrenergic receptors while adrenergic compounds bind to conserved extracellular regions of opioid receptors; opioid-like modules appear in both sets of receptors within key ligand-binding regions. Transmembrane regions associated with homodimerization of each class of receptors are also highly conserved across receptor types and implicated in heterodimerization. This conservation of multiple functional modules suggests opioid–adrenergic ligand and receptor co-evolution and provides mechanisms for explaining the evolution of their crosstalk. These modules also suggest the structure of a primordial receptor, providing clues for engineering receptor functions.

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Section: Evolutionary Models Of Resultsmentioning

confidence: 99%

Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

Root‐Bernstein¹,

Churchill²

2021

Life

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“…The adrenochrome was prepared as an aqueous solution at room temperature and either subjected to experimental analyses the same day or stored frozen at ¡80 ± C. Unlike epinephrine which is stabilized by bisul te, adrenochrome is converted to another compound by bisul te (Powell & Heacock, 1972), indicating that compounds that stabilize CA's don't behave the same for CA metabolites.…”

Section: Synthesis Of Adrenochrome and Adrenolutinmentioning

confidence: 99%

Analytical Methods to Detect the Autooxidation of Adrenolutin as a Step in Catecholamine Metabolism

Baskin¹,

Behonick²,

Schafer³

et al. 2000

Toxic Substance Mechanisms

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The acute hemodynamic effects of organophosphate (OP) intoxication include positive chronotropic and inotropic changes along with increases in intraventricular pressure and coronary blood ow. These observations are consistent with an enhanced sympathetic tone that correlates neurogenic cardiomyopathy to adrenergic overactivity and subsequent, focal catecholamine (CA) release and cellular oxidative stress. Several mechanisms have been proposed to explain the cardiotoxicity associated with elevated CA concentrations. However, it is suggested that the oxidative metabolites of CA's, rather than (or in addition to) the parent CA's per se, may initiate or be in part responsible for the cardiotoxicity. The chromatographic pro le of adrenochrome (1) and adrenolutin (2) (Figure 1) are described in this study in an isocratic, reverse phase HPLC method using UV/VIS and electrochemical (EC) detection.The aqueous adrenochrome standard shows a retention time of 1.9 minutes under employed conditions. Furthermore, using a ow rate of 0.6 mL/min and a UV/VIS detector set at a wavelength of 490 nm, several chromatographic peaks were detected, indicative of different species after injection of the aqueous adrenolutin standard. A similar multiple peak chromatographic pro le was observed with EC detection. We hypothesized from the literature and observed complexity of the chromatogram (i.e. multiple intermediate species of the adrenolutin) that adrenolutin is being autooxidized over time. Based upon EPR spin trapping, we found the generation of a carbon-centered radical at the C-2 position that will interact with oxygen to give an intermediate peroxy radical. This may be eventually transformed to 5,6-dihydroxy-1-methyl-2,3-indoledione. The production of these proposed carbon-and oxygen-centered radicals in the autooxidation of adrenolutin was con rmed by spin trapping experiments using the spin trap, ®-phenyl N-tert-butyl nitrone (PBN). When adrenolutin is dissolved in water at neutral pH in the presence of PBN, two different EPR spectra of PBN adducts are obtained. One observed PBN adduct has hyper ne splitting constants (hfsc's) of aN D 1.54 mT, aH D 0.40 mT, and a°H D 0.13 mT; the other observed PBN adduct has the following hfsc's a N D 1.50 mT and aH D 0.33 mT. The detection of these

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Indole Aldehydes and Ketones

Remers¹

1979

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Adrenochrome-thiol addition products

Cited by 9 publications

References 8 publications

Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

Analytical Methods to Detect the Autooxidation of Adrenolutin as a Step in Catecholamine Metabolism

Indole Aldehydes and Ketones

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