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Effect of capsazepine on the release of calcitonin gene‐related peptide‐like immunoreactivity (CGRP‐LI) induced by low pH, capsaicin and potassium in rat soleus muscle
Author(s) -
Santicioli Paolo,
Bianco Elena,
Figini Michela,
Bevan Stuart,
Maggi Carlo Alberto
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13854.x
Subject(s) - capsazepine , capsaicin , calcitonin gene related peptide , chemistry , medicine , endocrinology , trpv1 , pharmacology , receptor , neuropeptide , biochemistry , transient receptor potential channel
1 We have determined the effect of the competitive antagonist capsazepine at the capsaicin receptor on the release of calcitonin gene‐related peptide‐like immunoreactivity (CGRP‐LI) from rat isolated soleus muscle induced by capsaicin (1 μ m ), by superfusion with low pH medium (pH 5) or by KCl (80 m m ). 2 Each one of the three stimuli tested produced a marked CGRP‐LI release. Total evoked release (fmol g −1 ) was 482 ± 69, 169 ± 20 and 253 ± 43 for capsaicin, low pH medium and KCl, respectively. 3 Prior application of capsaicin (10 μ m for 30 min followed by 30 min of washout) to produce capsaicin desensitization in vitro abolished CGRP‐LI release induced by the three stimuli. 4 Capsazepine (1–100 μ m , 45 min preincubation) inhibited the evoked CGRP‐LI release. Capsaicin‐induced release was significantly inhibited by 77, 92 and 96% with 10, 30 and 100 μ m capsazepine, respectively. Low pH‐induced release was inhibited by 78, 84, 88 and 93% with 3, 10, 30 and 100 μ m capsazepine, respectively. KCl‐induced release was significantly inhibited by 55 and 93% with 30 and 100 μ m (but not with 10 μ m ) capsazepine, respectively. 5 These findings demonstrate that capsazepine prevents low pH‐ and capsaicin‐induced CGRP‐LI release from rat soleus muscle at concentrations which do not affect the release evoked by KCl. These findings imply a relationship between the action of low pH and activation of the capsaicin receptor. At high concentrations, capsazepine produces a nonspecific inhibitory effect on CGRP‐LI release from peripheral endings of the capsaicin‐sensitive primary afferent neurone.