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

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 muM), by superfusion with low pH medium (pH 5) or by KCl (80 mM). 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 muM 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 muM, 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 muM capsazepine, respectively. Low pH-induced release was inhibited by 78, 84, 88 and 93% with 3, 10, 30 and 100 muM capsazepine, respectively. KCl-induced release was significantly inhibited by 55 and 93% with 30 and 100 muM (but not with 10 muM) 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.