Ion channels involved in the release of calcitonin gene-related peptide by low pH, prostacyclin and capsaicin in the isolated guinea-pig heart.
The aim of this study was to characterise the release of calcitonin gene-related peptide (CGRP) by capsaicin, low pH and prostacyclin in terms of Ca2+ channel dependence, interactions with K(ATP) channels and the role of action potential propagation, in the isolated, perfused guinea-pig heart. The Ca2+ channel blocker omega-conotoxin reduced CGRP release evoked by 10(-7) M capsaicin, as well as CGRP release evoked by pH 7. CGRP release caused by capsaicin at low (10(-7) M) but not high (10(-6) M) concentrations was also attenuated by tetrodotoxin, indicating partial dependence on action potential propagation. CGRP release caused by prostacyclin was not altered by any of the tested drugs. The K(ATP) channel activator cromakalim and the K(ATP) channel blocker glibenclamide had no effect on CGRP release. Previous findings that low pH and capsaicin stimulate capsaicin-sensitive afferents in the isolated heart at least partly through common mechanisms are thus supported. Attenuation of capsaicin-evoked release of CGRP by tetrodotoxin suggests recruitment of additional nerve terminals by a local axon reflex.
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
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Källner
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Franco-Cereceda
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D015221:Potassium Channels; D011464:Epoprostenol; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin