Disease relevance of IB-MECA

• In addition, in melanoma tumor lesions derived from IB-MECA-treated mice, the expression level A3AR and the downstream key signaling proteins were modulated in the same pattern as was seen in vitro [1].
• Higher doses of IB-MECA were lethal in C57 mice subjected to renal ischemia [2].
• In addition, IB-MECA was able to inhibit forskolin-stimulated cAMP levels, which indicate the functional form of A3 receptor on the cell surface of these breast cancer cell lines [3].
• We examined the effect of the A3 adenosine receptor (AR) agonist IB-MECA on infarct size in an open-chest anesthetized dog model of myocardial ischemia-reperfusion injury [4].
• Weak activity of APNEA and IB-MECA discounts involvement of A3 receptors [5].

Psychiatry related information on IB-MECA

• IB-MECA significantly diminished scopolamine- and MK-801-induced impairment of spontaneous alternation in Y-maze and learning abilities in passive avoidance task as well as reduced higher locomotor activity in MK-801-treated group [6].

High impact information on IB-MECA

• METHODS: Rats received intraperitoneal injections of selective agonists of A1, A2a, and A3 adenosine receptors: 2-chloro-N(6)-cyclopentyladenosine (CCPA), CGS-21680 (CGS), or 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide (IB-MECA), respectively [7].
• Stimulation with the GiPCR ligands C5a and 1-deoxy-1-[6-[(3-iodophenyl)methyl]amino]-9H-purine-9-y1]-N-methyl-beta-D-ribofuranuronamide (IB-MECA) blocked the production of IL-12 p70 by human monocytes stimulated with LPS and IFN-gamma [8].
• Nebulized IB-MECA directly induced lung mast cell degranulation in wild-type mice while having no effect in A(3) receptor knockout mice [9].
• Accordingly, the level of beta-catenin responsive cell growth regulatory genes including c-myc and cyclin D1 was severely declined upon treatment of the cells with IB-MECA [10].
• Here we demonstrate the ability of IB-MECA to decrease the levels of protein kinase A, a downstream effector of cAMP, and protein kinase B/Akt in melanoma cells [10].

Chemical compound and disease context of IB-MECA

• A3 adenosine receptor agonist IB-MECA reduces myocardial ischemia-reperfusion injury in dogs [4].
• The A(1)R agonist N(6)-cyclopentyladenosine (CPA), the A(2A)R agonist CGS21680 [2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine], and the A(3)R agonist N(6)-(3-iodobenzyl)adenosine-5'-methyluronamide (IB-MECA) all prevented PE-induced hypertrophy [11].
• Furthermore, IB-MECA-induced increases in luciferase gene expression were sensitive to pertussis toxin, PD 98059, genistein, wortmannin and LY 294002 [12].

Biological context of IB-MECA

• Evaluation of beta-catenin, a key component of Wnt signaling pathway which, upon phosphorylation by GSK-3beta rapidly ubiquitinates, showed a substantial decrease in its level after IB-MECA treatment [10].
• In addition, DNA breaks in cardiomyocytes undergoing apoptosis following treatment by IB-MECA were identified in situ using the nick end labeling of DNA ("TUNEL"-like) assay [13].
• This result was further corroborated by showing that the two selective A1 and A3 receptor agonists, N-cyclopentyladenosine (CPA) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide (IB-MECA) respectively, induced bone marrow cell proliferation in a manner similar to adenosine [14].
• Administration of IB-MECA had no effect on any hemodynamic parameter measured including heart rate, first derivative of left ventricular pressure, aortic pressure, LAD coronary blood flow, or coronary collateral blood flow [4].
• 2. Intradermal (i.d.) injection of adenosine and analogues induced increased microvascular permeability in a dose-dependent manner (IB-MECA > NECA > CPA > adenosine) [15].

Anatomical context of IB-MECA

• The IB-MECA-induced mesangial cell death was due to apoptosis [16].
• All the compounds proved to be full antagonists in a specific functional model where the inhibition of cAMP generation by IB-MECA was measured in membranes of CHO cells stably transfected with the human A(3) receptor [17].
• IB-MECA, at 1-100 microM, resulted in a significant cell growth inhibition (P < 0.05) which reached the maximum at 48 h, in the cell lines [3].
• Increased cAMP was detected in neutrophils treated with CGS 21680 and IB-MECA (1 microM) [18].
• In rats treated with capsaicin to destroy sensory neurons, the response to higher doses of adenosine, CPA and NECA, but not IB-MECA, was significantly inhibited [15].

Associations of IB-MECA with other chemical compounds

• METHODS: Cultured mouse mesangial cell were incubated in the presence or absence of ADO or ADO receptor agonists (R-PIA, NECA, IB-MECA, CGS26180) or antagonists (DPCPX, DPSPX, MRS1191) for 48 hours [16].
• RESULTS: ADO and the A3 ADO receptor agonist IB-MECA induced mesangial cell death, which was markedly attenuated by the A3 receptor antagonist MRS1191 [16].
• Moreover, both CGS21680 and IB-MECA but not CPA decreased the mitochondrial membrane potential when PE was present, similarly to that seen with diazoxide, and both agents inhibited PE-stimulated elevation in mitochondrial Ca(2+) [11].
• In Western blot experiments, ryanodine receptor phosphorylation on serine 2809 was not modified after perfusion with IB-MECA [19].

Gene context of IB-MECA

• The high affinity adenosine A3 receptor agonist IB-MECA (1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-beta-D-ribofuranuronamide) stimulated time (peak activation occurring after 5 min) and concentration-dependent (pEC50=9.0+/-0.2) increases in p42/p44 MAPK in CHO-A3 cells [12].
• Using ADO receptor-specific analogs, we showed that highly selective A3 agonist N6-(3-iodobenzyl)-adenosine-5'-N'-methyluronamide (IB-MECA) inhibited LPS-induced TF activity expression more potently than A1 agonist R-phenylisopropyladenosine (R-PIA) and A2 agonist CGS 2180 [20].
• Expression of iNOS mRNA and NO production were enhanced after 6 and 24 h respectively of IB-MECA treatment [21].
• In contrast, the selective A3 agonist IB-MECA (EC50 1 nmol/L) stimulated angiopoietin-2 expression [22].
• IB-MECA 100 microM downregulated HIAP1, NAIP and survivin mRNAs in HL-60, but not in HL-60R cells [23].

Analytical, diagnostic and therapeutic context of IB-MECA

• RESULTS: Perfusion with the A1>A3 agonist R-PIA and the A3>A1 agonist IB-MECA was associated with reduced [3H]ryanodine binding, due to reduced B(max) (by about 20%), whereas K(d) and Ca(2+)-dependence of the binding reaction were unaffected [24].
• An equivalent reduction in infarct size was observed when IB-MECA was administered immediately before reperfusion (13.1 +/- 3.9%) [4].
• Nevertheless, pretreatment with IB-MECA before coronary occlusion produced a marked reduction in infarct size ( approximately 40% reduction) compared with the control group (13.0 +/- 3.2% vs. 25.2 +/- 3.7% of the area at risk, respectively) [4].
• The highly selective A3AR agonist, IB-MECA was earlier shown to prevent the clinical and pathological manifestations of arthritis in experimental animal models of collagen and adjuvant induced arthritis (AIA) [25].
• RT-PCR experiments showed that ryanodine receptor gene expression was not affected by IB-MECA [19].

References