Effects of capsaicin and 5-HT3 antagonists on 5-hydroxytryptamine-evoked release of calcitonin gene-related peptide in the guinea-pig heart.
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 microM) 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 microM), but not 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 100 microM), sumatriptan (100 microM) or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 100 microM) evoked a release of CGRP-LI. Ondansetron (10 microM) or ICS205-930 (20 microM) completely abolished the 5-HT (100 microM)-evoked CGRP-LI release. 4. In the isolated electrically driven left atria of the guinea-pig 5-HT (1-10 microM) and CPD (3-100 microM) produced a positive inotropic response, which was abolished by capsaicin pretreatment. 8-OH-DPAT (10 microM) and DOI (10 microM) were inactive. Ondansetron inhibited the response to 5-HT with a pA2 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-HT3 antagonists.
Tramontana
M
M
Institute of Internal Medicine IV, University of Florence, Italy.
Giuliani
S
S
Del Bianco
E
E
Lecci
A
A
Maggi
C A
CA
Evangelista
S
S
Geppetti
P
P
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009411:Nerve Endings / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D010477:Perfusion; D010525:Peripheral Nerves / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*
D002316:Cardiotonic Agents; D012702:Serotonin Antagonists; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin