Anti-inflammatory activity of non-nucleoside adenosine deaminase inhibitor FR234938

Kuno, Miyuki; Seki, Nobuo; Tsujimoto, Susumu; Nakanishi, Isao; Kinoshita, Takayoshi; Nakamura, Katsuya; Terasaka, Tadashi; Nishio, Nobuya; Sato, Akihiro; Fujii, Takashi

doi:10.1016/j.ejphar.2006.01.042

Cited by 41 publications

(25 citation statements)

References 45 publications

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“…Although it is present at low concentrations in the extracellular space, stressful conditions, such as inflammation and hypoxia, can markedly increase its extracellular level up to the micromolar range [13,24,27,28,44,48]. Adenosine binds to four different types of G proteincoupled cell surface receptors referred to as A 1 R, A 2A R, A 2B R and A 3 R, each of which has a unique pharmacological profile, tissue distribution and signalling pathway [18].…”

Section: Introductionmentioning

confidence: 99%

Adenosine A2A agonist and A2B antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation

Michael

Warstat

Michel

et al. 2009

Purinergic Signalling

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Adenosine can show anti-inflammatory as well as pro-inflammatory activities. The contribution of the specific adenosine receptor subtypes in various cells, tissues and organs is complex. In this study, we examined the effect of the adenosine A 2A receptor agonist CGS 21680 and the A 2B R antagonist PSB-1115 on acute inflammation induced experimentally by 2,4,6-trinitrobenzenesulfonic acid (TNBS) on rat ileum/jejunum preparations. Preincubation of the ileum/jejunum segments with TNBS for 30 min resulted in a concentration-dependent inhibition of acetylcholine (ACh)-induced contractions. Pharmacological activation of the A 2A R with CGS 21680 (0.1-10 µM) preincubated simultaneously with TNBS (10 mM) prevented concentration-dependently the TNBS-induced inhibition of the ACh contractions. Stimulation of A 2B R with the selective agonist BAY 60-6583 (10 µM) did neither result in an increase nor in a further decrease of ACh-induced contractions compared to the TNBS-induced inhibition. The simultaneous pre-incubation of the ileum/jejunum segments with TNBS (10 mM) and the selective A 2B R antagonist PSB-1115 (100 µM) inhibited the contractiondecreasing effect of TNBS. The effects of the A 2A R agonist and the A 2B R antagonist were in the same range as the effect induced by 1 µM methotrexate. The combination of the A 2A R agonist CGS 21680 and the A 2B R antagonist PSB-1115 at subthreshold concentrations of both agents found a significant amelioration of the TNBS-diminished contractility. Our results demonstrate that the activation of A 2A receptors or the blockade of the A 2B receptors can prevent the inflammation-induced disturbance of the AChinduced contraction in TNBS pre-treated small intestinal preparations. The combination of both may be useful for the treatment of inflammatory bowel diseases.

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Section: Introductionmentioning

confidence: 99%

Adenosine A2A agonist and A2B antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation

Michael

Warstat

Michel

et al. 2009

Purinergic Signalling

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“…Indeed, adenosine concentration in the extracellular space increases under conditions of inflammation [19]. As indicated above, it is well established that intestinal inflammation coincides with decreased SERT activity.…”

Section: Discussionmentioning

confidence: 79%

“…In the GI tract, adenosine has been demonstrated to modulate neurotransmission [17] and to be involved in a variety of intestinal functions [18]. Although adenosine is present at low concentrations in the extracellular space, adenosine availability increases under conditions of cellular stress, hypoxia and inflammation [19]. However, the role of adenosine in inflammatory processes is contradictory.…”

Section: Introductionmentioning

confidence: 99%

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

Matheus¹,

Mendoza²,

Iceta³

et al. 2009

Biochemical Pharmacology

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Serotonin plays a critical role in the regulation of intestinal physiology. The serotonin transporter (SERT) expressed in the intestinal epithelium determines 5-HT availability and activity. The serotoninergic system and SERT activity have been described as being altered in chronic intestinal pathologies such as inflammatory diseases. Adenosine has also been shown to be involved in a variety of intestinal functions and to play a central role in the regulation of inflammatory responses of injured tissue. Since the modulation of SERT by adenosine in the intestine remains unknown, the aim of the present work was to study the effect of adenosine on SERT activity and expression and to determine the molecular mechanism involved. The study has been carried out using human enterocyte-like Caco-2 cells which endogenously express SERT. The results show that adenosine diminishes SERT activity in both the apical and basal membranes by acting in the intrinsic molecule with no alteration of either SERT mRNA or protein levels. The effect of adenosine appears to be mediated by A 2 receptors and activation of the cAMP/PKA signalling pathway. Moreover, the adenosine effect did not seem to involve the activation of AMP activated protein kinase. Adenosine effects are reached at high concentrations, which suggests that adenosine modulation of SERT may be significant under conditions of inflammation and tissue injury.

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“…Níveis elevados de adenosina são produzidos por osteoprogenitores e outras células da medula óssea e seu efeito antiinflamatório sob condições de estresse celular já é estabelecido (Kuno, Seki et al 2006).…”

Section: Mfap4 (Microfibrillar-associated Protein 4): O Geneunclassified

“…Assim, trabalhos mostram que o tratamento de células com inibidores da ADA potencializam o efeito antiinflamatório da adenosina (Kuno, Seki et al 2006); (Antonioli, Fornai et al 2007). Assim, a diminuição da expressão do gene ADA observada em nossos pacientes, seria um mecanismo protetor do osso contra a atividade osteoclástica gerada pelo aumento do processo de reparação óssea, na tentativa de coordenar uma resposta compensatória dos osteoblastos na síntese de matriz óssea e assim, restabelecer a homeostase óssea.…”

Section: Mfap4 (Microfibrillar-associated Protein 4): O Geneunclassified

Análise da Expressão Gênica Durante a Diferenciação Osteogênica de Células Mesenquimais Estromais de Medula Óssea de Pacientes Portadores de Osteogênese Imperfeita

Kaneto¹

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Anti-inflammatory activity of non-nucleoside adenosine deaminase inhibitor FR234938

Cited by 41 publications

References 45 publications

Adenosine A2A agonist and A2B antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation

Adenosine A2A agonist and A2B antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

Análise da Expressão Gênica Durante a Diferenciação Osteogênica de Células Mesenquimais Estromais de Medula Óssea de Pacientes Portadores de Osteogênese Imperfeita

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