PGE2 increases substance P release from renal pelvic sensory nerves via activation of N-type calcium channels

Abstract

Activation of renal pelvic sensory nerves by increased pelvic pressure results in a renal pelvic release of substance P that is dependent on intact prostaglandin synthesis. An isolated renal pelvic wall preparation was used to examine whether PGE2increases the release of substance P from renal pelvic sensory nerves and by what mechanisms. The validity of the model was tested by examining whether 50 mM KCl increased substance P release from the pelvic wall. Fifty millimolar KCl produced an increase in substance P release, from 9.6 ± 1.6 to 26.8 ± 4.0 pg/min, P < 0.01, that was blocked by the L-type calcium blocker verapamil (10 μM). PGE2 (0.14 μM) increased the release of substance P from the pelvic wall from 8.9 ± 0.9 to 20.6 ± 3.3 pg/min, P < 0.01. PGE2 failed to increase substance P release in a calcium-free medium. The PGE2-induced substance P release was blocked by the N-type calcium blocker ω-conotoxin (0.1 μM) but was unaffected by verapamil. In conclusion, PGE2 increases the release of substance P from renal pelvic sensory nerves by a calcium-dependent mechanism that requires influx of calcium via N-type calcium channels.