Dual action of palmitoyl trifluoromethyl ketone (PACOCF3) on Ca2+ signaling: activation of extracellular Ca2+ influx and alteration of ATP- and bradykinin-induced Ca2+ responses in Madin Darby canine kidney cells.
The effect of the phospholipase A2 inhibitor palmitoyl trifluoromethyl ketone (PACOCF3) on Ca2+ signaling in Madin Darby canine kidney (MDCK) cells was examined using fura-2 as the fluorescent Ca2+ indicator. At a concentration of 20 microM, PACOCF3 did not change basal cytosolic free calcium concentrations ([Ca2+]i), but at concentrations of 50-250 microM PACOCF3 induced an increase in [Ca2+]i by activating extracellular Ca2+ entry which was partly suppressed by 50 microM La3+. The effect of PACOCF3 was abolished by removal of extracellular Ca2+. PACOCF3 (10 microM) enhanced both the peak value and the area under the curve of the [Ca2+]i increase induced by 10 microM ATP and 1 microM bradykinin by potentiating extracellular Ca2+ influx without affecting internal Ca2+ release. Several other phospholipase A2 inhibitors had no effect on basal [Ca2+]i or agonist-induced [Ca2+]i increases. Collectively, the results suggest that PACOCF3 alters Ca2+ signaling in renal tubular cells in a manner independent of phospholipase A2 inhibition.
Jan
C R
CR
Department of Medical Education and Research, Veterans General Hospital-Kaohsiung, Taiwan. crjan@isca.vghks.gov.tw
Chou
K J
KJ
Lee
K C
KC
Wang
J L
JL
Tseng
L L
LL
Cheng
J S
JS
Chen
W C
WC
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007659:Ketones / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000502:physiology; D054467:Phospholipases A2
D004791:Enzyme Inhibitors; D007659:Ketones; C109341:palmitoyl trifluoromethyl ketone; D007811:Lanthanum; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D054467:Phospholipases A2; D001920:Bradykinin; D002118:Calcium