Effect of dihydropyridines on the full-length human P2X5 receptor

Abstract

The P2X5 receptor, an ATP-gated cation channel, is believed to be involved in tumor development, inflammatory bone loss and inflammasome activation after bacterial infection. Therefore, it is a worthwhile pharmacological target to treat the corresponding diseases. Here, we investigated the effects of dihydropyridines on the human full length P2X5 receptor (hP2X5FL) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage clamp method. Agonist dependency, kinetics and permeation behavior were similar to hP2X5FL expressed in HEK293 or 1321N1 cells. Of 7 commercially available and 4 newly synthesized dihydropyridines tested, only amlodipine exerted an inhibitory effect, but only at a high concentration of 300 µM. Isradipine and even more nimodipine stimulated ATP-induced currents in the low micromolar range. We conclude that dihydropyridines are not suited as antagonistic agents on hP2X5, but that a side effect of nimodipine therapy could be a stimulatory effect on inflammatory processes.