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Prostacyclin activates tachykinin release from capsaicin‐sensitive afferents in guinea‐pig bronchi through a ruthenium red‐sensitive pathway
Author(s) -
Mapp Cristina Elisabetta,
Fabbri Leonardo Michele,
Boniotti Anna,
Maggi Carlo Alberto
Publication year - 1991
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.1476-5381.1991.tb12383.x
Subject(s) - ruthenium red , capsaicin , neurokinin a , substance p , tachykinin receptor , chemistry , acetylcholine , guinea pig , desensitization (medicine) , medicine , prostacyclin , contraction (grammar) , endocrinology , pharmacology , receptor , neuropeptide , biology , calcium , biochemistry
1 We have investigated the ability of prostacyclin (PGI 2 ) to contract guinea‐pig isolated bronchi and the possible involvement of capsaicin‐sensitive primary afferents in the response to PGI 2 . 2 PGI 2 (0.1–100 μ m ) produced concentration‐dependent contractions of the guinea‐pig isolated bronchi. In vitro capsaicin desensitization (10 μ m for 30 min followed by washing) significantly reduced the PGI 2 ‐induced contraction at all concentrations tested. A capsaicin‐resistant component of contraction (40–60% of the overall response) was also evident. 3 Ruthenium red (3 μ m ), an inorganic dye which acts as a selective functional antagonist of capsaicin, significantly decreased PGI 2 ‐induced contractions, without affecting the response to substance P, neurokinin A or acetylcholine. 4 MEN 10, 207, (Tyr 5 , d ‐Trp 6,8,9 , Arg 10 )‐neurokinin A (4–10) (3 μ m ), a selective antagonist of NK 2 ‐tachykinin receptors, significantly decreased PGI 2 ‐induced contractions and neurokinin A‐induced contractions, without affecting the response to acetylcholine. 5 The effect of ruthenium red and MEN 10,207 on the one hand, and that of ruthenium red and capsaicin on the other was non additive. 6 These results indicate that PGI 2 ‐induced contraction of the guinea‐pig isolated bronchi involves two distinct mechanisms, one of which involves transmitter (tachykinins) release from peripheral endings of capsaicin‐sensitive primary afferents. In as much as PGI 2 ‐activation of primary afferents is sensitive to ruthenium red, we suggest that PGI 2 shares a common mechanism of tachykinin release with that activated by capsaicin.