Another learn more plasma membrane purine transporter exists because Plasmodium falciparum ENT1-knockout parasites survive at supraphysiological purine concentrations. The other three ENTs have not been characterized functionally. Codon-optimized Pf- (P. falciparum) and Pv- (Plasmodium vivax) ENT4 were expressed in Xenopus laevis oocytes and substrate transport was determined with radiolabelled substrates. ENT4 transported adenine and 2′-deoxyadenosine at the highest rate, with millimolar-range apparent affinity.

ENT4-expressing oocytes did not accumulate hypoxanthine, a key purine salvage pathway substrate, or AMP. Micromolar concentrations of the plant hormone cytokinin compounds inhibited both PfENT4 and PvENT4. In contrast with PfENT1, ENT4 interacted with the immucillin compounds in the millimolar range and was inhibited by 10 mu M dipyridamole.

Thus ENT4 is a purine transporter with unique substrate and inhibitor specificity. Its role in parasite physiology remains uncertain, but is likely to be significant because of the strong conservation of ENT4 homologues in Plasmodia genomes.”
“Visceral pain currently represents one of the most important pain treatment challenges in clinical practice, and investigators across the world are continuously designing and conducting numerous studies in search of new analgesics see more and new combination therapies. The current study assessed the analgesic effects of saline, pregabalin (2, 5, 17, 50, 100, and 200 mg/kg, i.p.) and morphine (0.25, 0.5, 1, 3 and 5 mg/kg) alone or in combination on acetic-acid induced abdominal contractions in mice. The number this website of writhes and

the inhibitory effects (as percentages, %E) were calculated as antinociception indexes. These indexes indicated that both pregabalin (Prg) and morphine (Mrp) produced dose-dependent antinociception. Pregabalin at 5 mg/kg (%E = 32.5 +/- 4.0) or 2 mg/kg (%E = 20.8 +/- 4.5) and morphine at 0.25 mg/kg (%E = 20.2 +/- 7.8) and 0.5 mg/kg (%E = 43.6 +/- 4.5) exhibited antinociceptive effects, and the combination of pregabalin and morphine produced significantly greater antinociceptive effects (%E = 62.4 +/- 5.8 for Prg5 + Mrp025; %E = 71.7 +/- 4.8 for Prg5 + Mrp0.5; and %E = 54.1 +/- 4.0 for Prg2 + Mrp0.25), although this enhancement was not observed when morphine was combined with 17 mg/kg pregabalin. Pre-treatment with 2 mg/kg (i.p.) naloxone did not affect increased analgesia when combined with these drugs. A dose-response curve was established for pregabalin at a fixed morphine dose and revealed that, at low doses, pregabalin dose-dependently enhanced the antinociceptive effects, while the opposite was true at high doses (17 and 25 mg/kg). In conclusion, pregabalin can produce levels of antinociception that are similar to those of morphine in acetic add-induced viscero-somatic pain.