Allopurinol blocks shock-wave-induced rises in cytosolic calcium levels in MDCK cells

Allopurinol has been reported to ameliorate the side effects in patients following shock wave lithotripsy (SWL); however, the mechanism has not been studied. We have examined the protective effect of allopurinol on Madin- Darby canine kidney (MDCK) cells after shock wave exposure (SWE) by determining the release of aspartate aminotransferase (ASAT) and lactate dehydrogenase (LD), and the resting cytosolic Ca²⁺ concentration ([Ca²⁺](i)). In SWE-treated cells, the release of ASAT and LD increased immediately, but largely transiently, by approximately 23% and 5-fold over control, respectively. Within 1-6 h after SWE there was a gradual rise in the resting [Ca²⁺](i) of 16-137% above control. Allopurinol did not affect the transient enzyme release but blocked the long-term rises in the resting [Ca²⁺](i). The transient changes in [Ca²⁺](i) evoked by two hormones, ATP and bradykinin, and a drug that releases Ca²⁺ from internal Ca²⁺ stores, thapsigargin, were only slightly affected in allopurinol-treated cells. We conclude that the protection conferred by allopurinol on patients treated with SWL might involve a direct protection of the kidney cells by maintaining a normal resting [Ca²⁺](i).