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Aims: This work investigated the effects of 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294) treatment on the contractile response of soleus (SOL) muscle from rats submitted to myocardial infarction (MI)., Main Methods: Following coronary artery ligation, LASSBio-294 (2mg/kg, i.p.) or vehicle was administrated once daily for 4 weeks., Key Findings: The run time to fatigue for sham rats was 17.9 ±2.6 min, and it was reduced to 3.3 ± 0.8 min (P<0.05) in MI rats. In MI rats treated with LASSBio-294, the time to fatigue was 15.1 ± 3.6 min. During the contractile test, SOL muscles from sham rats showed a response of 7.12 ± 0.54N/cm(2) at 60 Hz, which was decreased to 5.45 ± 0.49 N/cm(2) (P<0.05) in MI rats. The contractility of SOL muscles from the MI-LASSBio-294 group was increased to 9.01 ± 0.65N/cm(2). At 16 mM caffeine, the contractility was reduced from 2.31 ± 0.33 to 1.60 ± 0.21 N/cm(2) (P<0.05) in the MI group. In SOL muscles from MI-LASSBio-294 rats, the caffeine response was increased to 2.62 ± 0.33 N/cm(2). Moreover, SERCA2a expression in SOL muscles was decreased by 0.31-fold (31%) in the MI group compared to the Sham group (P<0.05). In the MI-LASSBio-294 group, it was increased by 1.53-fold (153%) compared to the MI group (P<0.05). Meanwhile, the nuclear density in SOL muscles was increased in the MI group compared to the Sham group. Treatment with LASSBio-294 prevented this enhancement of cellular infiltrate., Significance: LASSBio-294 treatment prevented the development of muscular fatigue and improved exercise intolerance in rats submitted to MI., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Previous data showed that prostaglandin E₂ (PGE₂) mediates the inhibitory effect of bradykinin (BK) on proximal tubule (PT) Na+-ATPase activity. The aim of this work was to investigate the molecular mechanisms involved in the effect of PGE₂ on PT Na+-ATPase. We used isolated basolateral membrane (BLM) from pig PT, which expresses several components of different signaling pathways. The inhibitory effect of PGE₂ on PT Na+-ATPase activity involves G-protein and the activation of protein kinase A (PKA) because: (1) PGE₂ increased [³⁵S]GTPγS binding; (2) GDPβS abolished the inhibitory effect of PGE₂; (3) PGE₂ increased PKA activity; (4) the inhibitory effect of PGE₂ was abolished by PKA inhibitor peptide. We observed that the PKA-mediated inhibitory effect of PGE₂ on PT Na+-ATPase activity requires previous activation of protein kinase C. In addition, we observed that PGE₂ stimulates Ca²+-independent phospholipase A₂ activity representing an important positive feedback to maintain the inhibition of the enzyme. These results open new perspectives to understanding the mechanism involved in the effect of PGE₂ on proximal tubule sodium reabsorption., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In this work, the metabolism of adenosine by isolated BLM associated-enzymes and the implications of this process for the cAMP-signaling pathway are investigated. Inosine was identified as the major metabolic product, suggesting the presence of adenosine deaminase (ADA) activity in the BLM. This was confirmed by immunoblotting and ADA-specific enzyme assay. Implications for the enzymatic deamination of adenosine on the receptor-modulated cAMP-signaling pathway were also investigated. We observed that inosine induced a 2-fold increase in [(35)S] GTPgammaS binding to the BLM and it was inhibited by 10(-6)M DPCPX, an A(1) receptor-selective antagonist. Inosine (10(-7)M) inhibited protein kinase A activity in a DPCPX-sensitive manner. Molecular association between ADA and G(alphai-3) protein-coupled A(1) receptor was demonstrated by co-immunoprecipitation assay. These data show that adenosine is deaminated by A(1) receptor-associated ADA to inosine, which in turn modulates PKA in the BLM through A(1) receptor-mediated inhibition of adenylyl cyclase.