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.
Jan
C R
CR
Department of Medical Education and Research, Veterans General Hospital-Kaohsiung, Taiwan, Republic of China. crjan@isca.vghks.gov.tw
Chen
W C
WC
Lee
Y H
YH
Huang
J K
JK
Ou
H C
HC
Tseng
C J
CJ
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D019220:High-Energy Shock Waves / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism
D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D002118:Calcium