Purinergic signalling is involved in the malaria parasite Plasmodium falciparum invasion to red blood cells.

UNLABELLED: Plasmodium falciparum, the most important etiological agent of human malaria, is endowed with a highly complex cell cycle that is essential for its successful replication within the host. A number of evidence suggest that changes in parasite Ca(2+) levels occur during the intracellular cycle of the parasites and play a role in modulating its functions within the RBC. However, the molecular identification of Plasmodium receptors linked with calcium signalling and the causal relationship between Ca(2+) increases and parasite functions are still largely mysterious. We here describe that increases in P. falciparum Ca(2+) levels, induced by extracellular ATP, modulate parasite invasion. In particular, we show that addition of ATP leads to an increase of cytosolic Ca(2+) in trophozoites and segmented schizonts. Addition of the compounds KN62 and Ip5I on parasites blocked the ATP-induced rise in [Ca(2+)](c). Besides, the compounds or hydrolysis of ATP with apyrase added in culture drastically reduce RBC infection by parasites, suggesting strongly a role of extracellular ATP during RBC invasion. The use of purinoceptor antagonists Ip5I and KN62 in this study suggests the presence of putative purinoceptor in P. falciparum. In conclusion, we have demonstrated that increases in [Ca(2+)](c) in the malarial parasite P. falciparum by ATP leads to the modulation of its invasion of red blood cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11302-010-9202-y) contains supplementary material, which is available to authorized users.

P2Y(1) receptor activation enhances the rate of rat pinealocyte-induced extracellular acidification via a calcium-dependent mechanism.

Pineal gland G-protein coupled P2Y(1) receptors potentiate noradrenaline-induced N'-acetylserotonin production, a long term response which occurs after 5 h incubation. In the current study we show that a short-term effect of stimulation of P2Y(1) receptors is the increase in extracellular acidification rate (ECAR), which is mediated by an increase in intracellular calcium concentration ([Ca(2+)](i)). The pD(2) values for ATP (3.06 +/- 0.12)-induced ECAR increase was significantly smaller (p < 0.01) than that for ADP (3.64 +/- 0.18), 2MeSATP (3.56 +/- 0.02) and 2MeSADP (3.65 +/- 0.13). The selective P2Y(1) receptor antagonists A3'P-5'P and A3'P-5'PS inhibited the increase in ECAR-induced by ADP. Clamping [Ca(2+)](i) with BAPTA (30 and 50 micromol/l) led to inhibition of ADP-induced increase in ECAR. Agonist and antagonist data indicate P2Y(1) activation leads to a [Ca(2+)](i)-dependent acidification of the extracellular medium.