Agmatine: clinical applications after 100 years in translation

Piletz, John E.; Arıcıoğlu, Feyza; Cheng, Juei Tang; Fairbanks, Carolyn A.; Gilad, Varda H.; Haenisch, Britta; Halaris, Angelos; Hong, Samin; Lee, Jong Eun; Jin, Li; Liu, Ping; Molderings, Gerhard J.; Rodrigues, Ana Lúcia S.; Satriano, Joseph; Seong, Gong Je; Wilcox, George L.; Wu, Ning; Gilad, Gad M.

doi:10.1016/j.drudis.2013.05.017

Cited by 222 publications

(193 citation statements)

References 124 publications

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“…Another notable amino acid metabolite, agmatine (decarboxylated arginine), positively modulates norepinephrine-mediated inhibition of norepinephrine release at the a 2 -AR, although multiple modes of interaction involving both the orthosteric and an allosteric site on this receptor have also been proposed (Molderings et al, 2000). Biosynthesis of agmatine, and subsequent activation of a 2 -AR, may have cardiovascular protective effects, as well as anticonvulsant, antineurotoxic, and antidepressant actions (Piletz et al, 2013).…”

Section: Amino Acids and Peptides As Allosteric Modulatorsmentioning

confidence: 99%

Endogenous Allosteric Modulators of G Protein–Coupled Receptors

Westhuizen

Valant

Sexton

et al. 2015

J Pharmacol Exp Ther

132

131

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Section: Amino Acids and Peptides As Allosteric Modulatorsmentioning

confidence: 99%

Endogenous Allosteric Modulators of G Protein–Coupled Receptors

Westhuizen

Valant

Sexton

et al. 2015

J Pharmacol Exp Ther

132

131

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“…However, it is normally present only in trace amounts -tissue concentrations are usually below 1 μM [56]. It should also be noted that this system requires the expression of no additional proteins supplied in trans.…”

Section: Discussionmentioning

confidence: 99%

An agmatine-inducible system for the expression of recombinant proteins in Enterococcus faecalis

et al. 2014

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Background: Scientific interest in Enterococcus faecalis has increased greatly over recent decades. Some strains are involved in food fermentation and offer health benefits, whereas others are vancomycin-resistant and cause infections that are difficult to treat. The limited availability of vectors able to express cloned genes efficiently in E. faecalis has hindered biotechnological studies on the bacterium's regulatory and pathogenicity-related genes. The agmatine deiminase (AGDI) pathway of E. faecalis, involved in the conversion of agmatine into putrescine, is driven by a response inducer gene aguR.Results: This study describes that the exposure to the induction factor (agmatine) results in the transcription of genes under the control of the aguB promoter, including the aguBDAC operon. A novel E. faecalis expression vector, named pAGEnt, combining the aguR inducer gene and the aguB promoter followed by a cloning site and a stop codon was constructed. pAGEnt was designed for the overexpression and purification of a protein fused to a 10-amino-acid His-tag at the C-terminus. The use of GFP as a reporter of gene expression in E. faecalis revealed that under induction with 60 mM agmatine, fluorescence reached 40 arbitrary units compared to 0 in uninduced cells. Conclusion: pAGEnt vector can be used for the overexpression of recombinant proteins under the induction of agmatine in E. faecalis, with a close correlation between agmatine concentration and fluorescence when GFP was used as reporter.

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“…Idazoxan and agmatine inhibited the expression of inducible nitric oxide synthase in vitro (Regunathan et al 1999), although agmatine is also capable to interact with multiple other molecular targets, which can contribute to its cyto-and organoprotective effects (reviewed recently by Piletz et al 2013). Furthermore, various novel imidazoline scaffolds were shown to inhibit human proteasome (Lansdell et al 2013), which in turn prevented NF-κB mediated gene transcription in cell cultures (Sharma et al 2004;Kahlon et al 2009) and the production of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in human blood (Kahlon et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Analysing the effect of I1 imidazoline receptor ligands on DSS-induced acute colitis in mice

et al. 2016

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Imidazoline receptors (IRs) have been recognized as promising targets in the treatment of numerous diseases, and moxonidine and rilmenidine, agonists of I1-IRs are widely used as antihypertensive agents. Some evidence suggests that IR ligands may induce anti-inflammatory effects acting on I1-IRs or other molecular targets, which could be beneficial in patients with inflammatory bowel disease (IBD). On the other hand, several IR ligands may stimulate also alpha2-adrenoceptors, which was earlier shown to inhibit, but in more recent studies to rather aggravate colitis. Hence, this study aimed to analyse for the first time the effect of various I1-IR ligands on intestinal inflammation. Colitis was induced in C57BL/6 mice by adding dextran sulfate sodium (DSS) to the drinking water for 7 days. Mice were treated daily with different IR ligands; moxonidine and rilmenidine (I1-IR agonists), AGN 192403 (highly selective I1-IR ligand, putative antagonist), efaroxan (I1-IR antagonist), as well as with the endogenous IR agonists agmatine and harmane. It was found that moxonidine and rilmenidine at clinically relevant doses, similarly to the other IR ligands, do not have a significant impact on the macroscopic and histological signs of DSS-evoked inflammation. Likewise, colonic myeloperoxidase and serum interleukin-6 levels remained unchanged in response to these agents. Thus, our study demonstrates that imidazoline ligands do not influence significantly the severity of DSS-colitis in mice and suggest that they probably neither affect the course of IBD in humans. However, the translational value of these findings needs to be verified with other experimental colitis models and human studies.

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Agmatine: clinical applications after 100 years in translation

Cited by 222 publications

References 124 publications

Endogenous Allosteric Modulators of G Protein–Coupled Receptors

Endogenous Allosteric Modulators of G Protein–Coupled Receptors

An agmatine-inducible system for the expression of recombinant proteins in Enterococcus faecalis

Analysing the effect of I1 imidazoline receptor ligands on DSS-induced acute colitis in mice

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