Trace amine metabolism in Parkinson's disease: Low circulating levels of octopamine in early disease stages

D’Andrea, Giovanni; Nordera, G. P.; Pizzolato, Gilberto; Bolner, Andrea; Colavito, Davide; Flaibani, Raffaella; Leon, Alberta

doi:10.1016/j.neulet.2009.12.025

Cited by 32 publications

(27 citation statements)

References 23 publications

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“…Such compensation appears short‐lived because there is a decline in noradrenergic reuptake in the first few years of PD, suggesting an exhaustion of any noradrenergic compensation 8. Peripheral blood levels of noradrenaline are not reduced in de novo patients with PD but decline as the disease progresses 9–11. These studies suggest that the central noradrenergic deficit is not an early feature in PD, a finding consistent with the variability documented in the degree of neuronal loss in pathologically‐confirmed cases 12–16.…”

supporting

confidence: 62%

An evidence base for noradrenergic deficits in Parkinson's disease

Halliday

2012

Movement Disorders

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supporting

confidence: 62%

An evidence base for noradrenergic deficits in Parkinson's disease

Halliday

2012

Movement Disorders

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“…It has also been proposed that TAAR are involved as neuromodulators in brain [2], [6]. In accordance, TAAR are postulated to be linked with neurological disorders like bipolar disease [7], [8], schizophrenia [9], [10], depression and Parkinson's disease [11], [12]. In consequence, TAAR are potential new important therapeutic targets for several pathological situations [13], [14].…”

Section: Introductionmentioning

confidence: 88%

Differential Modulation of Beta-Adrenergic Receptor Signaling by Trace Amine-Associated Receptor 1 Agonists

et al. 2011

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Trace amine-associated receptors (TAAR) are rhodopsin-like G-protein-coupled receptors (GPCR). TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR), phenylethylamine (PEA), octopamine (OA), but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1) and 2 (ADRB2) have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR) octopamine (OAR), ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes.

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“…9, 10 Octopamine is found in trace amounts in vertebrates and as a trace amine may play a role in depression and other psychiatric disorders. 11-13 Octopamine in invertebrates is also analogous in function to norepinephrine in vertebrates. For example, octopamine release can be stimulated by nicotine application in Drosophila, similar to norepinephrine release in mammals.…”

Section: Introductionmentioning

confidence: 99%

Fast-Scan Cyclic Voltammetry (FSCV) Detection of Endogenous Octopamine in Drosophila melanogaster Ventral Nerve Cord

Pyakurel

Champaloux

Venton

2016

ACS Chem. Neurosci.

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Octopamine is an endogenous biogenic amine neurotransmitter, neurohormone, and neuromodulator in invertebrates, and has functional analogy with norepinephrine in vertebrates. Fast-scan cyclic voltammetry (FSCV) can detect rapid changes in neurotransmitters, but FSCV has not been optimized for octopamine detection in situ. The goal of this study was to characterize octopamine release in the ventral nerve cord of Drosophila larvae for the first time. An FSCV waveform was optimized so that the potential for octopamine oxidation would not be near the switching potential where interferences can occur. Endogenous octopamine release was stimulated by genetically inserting either the ATP sensitive channel, P2X2, or the red-light sensitive channelrhodopsin, CsChrimson, into cells expressing tyrosine decarboxylase (TDC), an octopamine synthesis enzyme. To ensure that release is due to octopamine and not the precursor tyramine, the octopamine synthesis inhibitor disulfiram was applied, and the signal decreased by 80%. Stimulated release was vesicular and a 2 s continuous light stimulation of CsChrimson evoked 0.22 ± 0.03 μM of octopamine release in the larval VNC. Repeated stimulations were stable with 2 or 5 minutes interstimulation times. With pulsed stimulations, the release was dependent on the frequency of applied light pulse. An octopamine transporter has not been identified, and blockers of the dopamine transporter and serotonin transporter had no significant effect on the clearance time of octopamine, suggesting they do not take up octopamine. This study shows that octopamine can be monitored in Drosophila, facilitating future studies of how octopamine release functions in the insect brain.

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Trace amine metabolism in Parkinson's disease: Low circulating levels of octopamine in early disease stages

Cited by 32 publications

References 23 publications

An evidence base for noradrenergic deficits in Parkinson's disease

An evidence base for noradrenergic deficits in Parkinson's disease

Differential Modulation of Beta-Adrenergic Receptor Signaling by Trace Amine-Associated Receptor 1 Agonists

Fast-Scan Cyclic Voltammetry (FSCV) Detection of Endogenous Octopamine in Drosophila melanogaster Ventral Nerve Cord

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