PGE2 increases substance P release from renal pelvic sensory nerves via activation of N-type calcium channels.
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 PGE2 increases 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 microM). PGE2 (0.14 microM) 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 omega-conotoxin (0.1 microM) 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.
Kopp
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UC
Department of Internal Medicine, Department of Veterans Affairs Medical Center and University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. ukopp@blue.weeg.uiowa.edu
Cicha
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MZ
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism*; D007682:Kidney Pelvis / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013373:Substance P; D011189:Potassium Chloride; D020866:omega-Conotoxin GVIA; D014700:Verapamil; D015232:Dinoprostone; D002118:Calcium