Dopamine release is regulated by presynaptic dopamine receptors and interactions between adenosine and dopamine receptors have been well documented. In the present study, dopamine release from isolated striatal slices from Wistar rats was measured using fast cyclic voltammetry. Single-pulse stimulation (0.1 ms, 10 V) was applied every 5 min over a 2-h period. Superfusion with the adenosine (A)(1) receptor agonist N(6)-cyclopentyladenosine (CPA), but not the A(2) receptor agonist 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino]ethyl] phenyl]propanoic acid (CGS 21680), inhibited dopamine release in a concentration-dependent manner (IC(50) 3.80 x 10(-7) m; n = 10). The dose-response curve to CPA was shifted to the right (IC(50) 6.57 x 10(-6) m; n = 6, P < 0.05 vs. control) by the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Neither the D(1) agonist 6-chloro-APB nor the D(1) antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepine-7-ol (SCH 23390) altered dopamine release on their own. However, SCH 23390 (3 microm) significantly attenuated the response to CPA (IC(50) 1.44 x 10(-5) m; n = 6, P < 0.01 vs. control). Furthermore, the inhibitory effect of CPA was significantly increased in the presence of 6-chloro-APB (1 microm). In radioligand binding experiments, CPA interacted with high- and low-affinity states of [(3)H]DPCPX-lableled A(1) receptors. The high-affinity agonist binding to A(1) receptors was inhibited by the stable guanosine triphosphate analogue Gpp(NH)p. In contrast, neither the proportion nor the affinity of high-affinity A(1) receptors was altered by dopamine or SCH 23390. These results provide evidence that the inhibition of dopamine release by adenosine A(1) receptors is dependent, at least in part, on the simultaneous activation of D(1) dopamine receptors. While the mechanism underlying this interaction remains to be determined, it does not appear to involve an intramembrane interaction between A(1) and D(1) receptors.

BackgroundMetabolic syndrome (MS) is associated with increased cardiovascular risk. It is not clear whether myocardial changes showed in this syndrome, such as diastolic dysfunction, are due to the systemic effects of the syndrome, or to specific myocardial effects. ObjectivesCompare diastolic function, biomarkers representing extracellular matrix activity (ECM), inflammation and cardiac hemodynamic stress in patients with the MS and healthy controls. MethodsMS patients (n = 76) and healthy controls (n=30) were submitted to a clinical assessment, echocardiographic study, and measurement of plasma levels of metalloproteinase-9 (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP1), ultrasensitive-reactive-C-Protein (us-CRP), insulin resistance (HOMA-IR) and natriuretic peptide (NT-proBNP). ResultsMS group showed lower E' wave (10.1 ± 3.0 cm/s vs 11.9 ± 2.6 cm/s, p = 0.005), increased A wave (63.4 ± 14.1 cm/s vs. 53.1 ± 8.9 cm/s; p < 0.001), E/E' ratio (8.0 ± 2.2 vs. 6.3 ± 1.2; p < 0.001), MMP9 (502.9 ± 237.1 ng / mL vs. 330.4±162.7 ng/mL; p < 0.001), us-CRP (p = 0.001) and HOMA-IR (p < 0.001), but no difference for TIMP1 or NT-proBNP levels. In a multivariable analysis, only MMP9 was independently associated with MS. ConclusionMS patients showed differences for echocardiographic measures of diastolic function, ECM activity, us-CRP and HOMA-IR when compared to controls. However, only MMP9 was independently associated with the MS. These findings suggest that there are early effects on ECM activity, which cannot be tracked by routine echocardiographic measures of diastolic function.

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Background and aims: Childhood obesity and overweight predict short and long-term morbidity as well as obesity in adulthood. Evidence is not consistent about the association of breastfeeding and childhood overweight.