Calcitonin gene-related peptide: release by capsaicin and prolongation of the action potential in the guinea-pig heart.
The mechanisms underlying the stimulatory effects of capsaicin on the contractility of the guinea-pig heart were studied in vitro. Capsaicin (10(-7) to 10(-5) M) caused an increased overflow of immunoreactive material, suggesting release of calcitonin gene-related peptide (CGRP)-and neurokinin A (NKA)-like immunoreactivity (-LI), but not of neuropeptide Y (NPY)-LI from the isolated Langendorff-perfused whole heart. The capsaicin-induced release was calcium-dependent. During exposure to capsaicin, the heart rate was increased, while the contractile force was reduced. In addition to releasing CGRP and NKA-LI, potassium (60 mM) also increased the overflow of NPY-LI. The potassium-induced release of peptides was less calcium-dependent than the response to capsaicin. Considerably higher tissue levels of CGRP-LI were found in the atria (about 30 pmol g-1) than in the ventricles (about 10 pmol g-1). In experiments on the right atria using transmembrane action-potential recordings of myocytes, CGRP induced a prolongation of the action potential concomitantly with an increase in rate and contractile force, which was similar to the effect of noradrenaline. Furthermore, CGRP increased the contractile force and relaxation velocity of the electrically stimulated atria. Capsaicin (10(-7) M) also increased the duration of the atrial action potential. In conclusion, CGRP-like material is released by capsaicin from the isolated guinea-pig heart. Both CGRP and capsaicin prolong the plateau phase of the action potential of atrial myocytes. Therefore, the present data give further evidence that CGRP release from sensory nerves within the heart underlies the cardiostimulatory actions of capsaicin.
Franco-Cereceda
A
A
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Lundberg
J M
JM
Saria
A
A
Schreibmayer
W
W
Tritthart
H A
HA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D015288:Neurokinin A / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010477:Perfusion
D002316:Cardiotonic Agents; D009478:Neuropeptide Y; D009479:Neuropeptides; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin