Renal artery responses to trace amines: Multiple and differential mechanisms of action

Koh, Andy Hsien Wei; Chess-Williams, Russ; Lohning, Anna

doi:10.1016/j.lfs.2021.119532

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…This was done by examining the effect of EPPTB, a selective TAAR1 antagonist [29] that is structurally related to RO5263397 on TAAR1 agonist-mediated vasodilation in this preparation. EPPTB has been used in several investigations to determine the involvement or otherwise of TAAR1 in a variety of biological actions of trace amines centrally and peripherally [11,23,[30][31][32]. It has been reported that the affinity of EPPTB for TAAR1 exhibits species variation ranging from 0.9 nM in mice through 942 nM in rats and ≥5,000 nM in humans [20].…”

Section: Discussionmentioning

confidence: 99%

Vasodilator Effect of Trace Amines, 3-Iodothyronamine, and RO5263397 in the Rat Perfused Kidney: Comparison with Tryptamine

Jragh¹,

Chandrasekhar²,

Yousif³

et al. 2023

Pharmacology

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Introduction: Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors and are widely distributed in the body. Activation of TAAR1 by specific agonists can produce a variety of physiological effects centrally and peripherally. The objective of this study was to investigate the vasodilator effect of two selective TAAR1 agonists 3-iodothyronamine (T1AM) and RO5263397 in the isolated perfused rat kidney preparation. Methods: Kidneys were isolated and perfused with Krebs’ solution, gassed with 95% oxygen and 5% carbon dioxide, through the renal artery. Results: In preparations pre-constricted with methoxamine (5 × 10−6<sc>m</sc>), T1AM (10−10 – 10−6 mol), RO5263397 (10−10 – 10−6 mol), and tryptamine (10−10 – 10−6 mol) produced dose-dependent vasodilator responses. EPPTB (1 × 10−6<sc>m</sc>), a selective TAAR1 antagonist, had no effect on vasodilator responses induced by these agonists. A higher concentration of EPPTB (3 × 10−5<sc>m</sc>) produced a sustained increase in perfusion pressure but did not affect vasodilator responses to tryptamine, T1AM, and RO5263397. Agonist-induced vasodilator responses were slightly reduced by the removal of the endothelium but were not affected by L-NAME (1 × 10−4<sc>m</sc>), an inhibitor of nitric oxide synthesis. The vasodilator responses were significantly reduced by inhibiting calcium-activated (tetraethylammonium, 1 × 10−3<sc>m</sc>) and voltage-activated (4-AP, 1 × 10−3<sc>m</sc>) potassium channels. Tryptamine-, T1AM-, and RO5263397-induced vasodilator responses were significantly reduced by BMY7378, a 5-HT1A receptor antagonist. Conclusion: It was concluded that vasodilator responses produced by the TAAR1 agonists, T1AM, RO5263397, and tryptamine, were not mediated via TAAR1 but were probably via activation of 5-HT1A receptors.

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Section: Discussionmentioning

confidence: 99%

Vasodilator Effect of Trace Amines, 3-Iodothyronamine, and RO5263397 in the Rat Perfused Kidney: Comparison with Tryptamine

Jragh¹,

Chandrasekhar²,

Yousif³

et al. 2023

Pharmacology

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“…Moreover, intracellular glutathione depletion elicited by m-synephrine in calcium-tolerant freshly isolated cardiomyocytes was independent of α1 adrenoreceptor stimulation [ 92 ], showing that there are confounding factors related to the role of adrenergic receptor stimulation on synephrine’s toxicity. Binding to TAAR is being pointed as a possible mechanism of action for synephrine beyond adrenergic receptors [ 49 , 96 ].…”

Section: Synephrinementioning

confidence: 99%

Natural Sympathomimetic Drugs: From Pharmacology to Toxicology

Costa

Grando²,

Milandri³

et al. 2022

Biomolecules

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Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly by increasing endogenous catecholamine levels or mimicking their intracellular signaling pathways. Compounds from this group, both used therapeutically or abused, comprise endogenous catecholamines (such as adrenaline and noradrenaline), synthetic amines (e.g., isoproterenol and dobutamine), trace amines (e.g., tyramine, tryptamine, histamine and octopamine), illicit drugs (e.g., ephedrine, cathinone, and cocaine), or even caffeine and synephrine. In addition to the effects triggered by stimulation of the sympathetic system, the discovery of trace amine associated receptors (TAARs) in humans brought new insights about their sympathomimetic pharmacology and toxicology. Although synthetic sympathomimetic agents are mostly seen as toxic, natural sympathomimetic agents are considered more complacently in the terms of safety in the vision of the lay public. Here, we aim to discuss the pharmacological and mainly toxicological aspects related to sympathomimetic natural agents, in particular of trace amines, compounds derived from plants like ephedra and khat, and finally cocaine. The main purpose of this review is to give a scientific and updated view of those agents and serve as a reminder on the safety issues of natural sympathomimetic agents most used in the community.

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“…In another set of experiments the human colon responses to cumulative concentrations of 5-HT (0.1 µM-1 mM) were examined in the absence or in the presence of methysergide (10 µM). The concentrations of the drugs used were determined from the literature [28][29][30][31].…”

Section: Functional Studiesmentioning

confidence: 99%

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility

et al. 2021

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The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.

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Renal artery responses to trace amines: Multiple and differential mechanisms of action

Cited by 4 publications

References 25 publications

Vasodilator Effect of Trace Amines, 3-Iodothyronamine, and RO5263397 in the Rat Perfused Kidney: Comparison with Tryptamine

Vasodilator Effect of Trace Amines, 3-Iodothyronamine, and RO5263397 in the Rat Perfused Kidney: Comparison with Tryptamine

Natural Sympathomimetic Drugs: From Pharmacology to Toxicology

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility

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