Franco-Cereceda A, Lundberg J M, Saria A, Schreibmayer W, Tritthart H A
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Acta Physiol Scand. 1988 Feb;132(2):181-90. doi: 10.1111/j.1748-1716.1988.tb08316.x.
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.
在体外研究了辣椒素对豚鼠心脏收缩性的刺激作用机制。辣椒素（10⁻⁷至10⁻⁵M）导致免疫反应性物质溢出增加，提示降钙素基因相关肽（CGRP）和神经激肽A（NKA）样免疫反应性（-LI）释放，但从离体Langendorff灌注的全心中未释放神经肽Y（NPY）-LI。辣椒素诱导的释放是钙依赖性的。在暴露于辣椒素期间，心率增加，而收缩力降低。除了释放CGRP和NKA-LI外，钾（60 mM）也增加了NPY-LI的溢出。钾诱导的肽释放比辣椒素反应的钙依赖性小。心房中CGRP-LI的组织水平（约30 pmol g⁻¹）比心室中（约10 pmol g⁻¹）高得多。在使用心肌细胞跨膜动作电位记录的右心房实验中，CGRP诱导动作电位延长，同时心率和收缩力增加，这与去甲肾上腺素的作用相似。此外，CGRP增加了电刺激心房的收缩力和舒张速度。辣椒素（10⁻⁷M）也增加了心房动作电位的持续时间。总之，辣椒素从离体豚鼠心脏释放出CGRP样物质。CGRP和辣椒素都延长了心房肌细胞动作电位的平台期。因此，目前的数据进一步证明，心脏内感觉神经释放的CGRP是辣椒素心脏刺激作用的基础。
