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Effects of capsaicin and 5‐HT 3 antagonists on 5‐hydroxytryptamine‐evoked release of calcitonin gene‐related peptide in the guinea‐pig heart
Author(s) -
Tramontana Manuela,
Giuliani Sandro,
Bianco Elena,
Lecci Alessandro,
Maggi Carlo A.,
Evangelista Stefano,
Geppetti Pierangelo
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.tb12821.x
Subject(s) - calcitonin gene related peptide , capsaicin , guinea pig , medicine , endocrinology , chemistry , calcitonin , inotrope , pharmacology , receptor , neuropeptide
1 The effect of 5‐hydroxytryptamine (5‐HT) on the release of calcitonin gene‐related peptide (CGRP) was studied directly in the isolated perfused heart and indirectly in the isolated left atria of guinea‐pig. 2 5‐HT injection into the guinea‐pig isolated and perfused heart evoked a dose‐dependent (1–100 μ m ) release of CGRP‐like immunoreactivity (LI) that was abolished by in vitro pretreatment with capsaicin and was not affected by indomethacin. 3 Chlorophenyldiguanide (CPD, 100 μ m ), but not 8‐hydroxy‐dipropylaminotetralin (8‐OH‐DPAT, 100 μ m ), sumatriptan (100 μ m ) or 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI, 100 μ m ) evoked a release of CGRP‐LI. Ondansetron (10 μ m ) or ICS205‐930 (20 μ m ) completely abolished the 5‐HT (100 μ m )‐evoked CGRP‐LI release. 4 In the isolated electrically driven left atria of the guinea‐pig 5‐HT (1–10 μ m ) and CPD (3–100 μ m ) produced a positive inotropic response, which was abolished by capsaicin pretreatment. 8‐OH‐DPAT (10 μ m ) and DOI (10 μ m ) were inactive. Ondansetron inhibited the response to 5‐HT with a pA 2 of 6.50 (CL 6.08–6.91). 5 It is concluded that 5‐HT causes a release of CGRP in the whole heart and a positive inotropic response in the isolated atria of guinea‐pig. Both these effects are sensitive to capsaicin pretreatment and to 5‐HT 3 antagonists.