Franco-Cereceda A, Källner G, Lundberg J M
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
Eur J Pharmacol. 1993 Jul 20;238(2-3):311-6. doi: 10.1016/0014-2999(93)90862-c.
The present study aimed to evaluate the possible influence of the selective capsaicin antagonist, capsazepine, on the release of calcitonin gene-related peptide (CGRP)-like immunoreactivity from sensory nerves in the isolated perfused guinea-pig heart. Low-pH buffer (pH 7, 6, 5), capsaicin (10(-7) M), lactic acid (5, 20, 50 mM) and nicotine (10(-4) M) all evoked a clear-cut release of CGRP-like immunoreactivity. Incubation with capsazepine (10(-6) to 10(-5) M) significantly reduced the CGRP-like immunoreactivity release evoked by low pH, capsaicin and lactic acid (5 mM) but not that evoked by nicotine. Furthermore, the capsaicin-evoked stimulation of heart rate was inhibited by incubation with capsazepine. The inorganic dye, ruthenium red, which has previously been shown to attenuate capsaicin-, but not nicotine-induced CGRP release from the heart, also reduced the release of CGRP caused by low pH and lactic acid (5 mM). It is concluded that the CGRP-like immunoreactivity release evoked from the heart by low pH and lactic acid shares several characteristic features with the release evoked by capsaicin. Since tissue pH is low in myocardial ischaemia and this is well known to cause pain, the use of capsazepine to inhibit the function of C-fibre afferents may represent a novel principle to influence autonomic reflex reactions associated with cardiac pathological conditions.
本研究旨在评估选择性辣椒素拮抗剂辣椒平对离体灌流豚鼠心脏感觉神经中降钙素基因相关肽（CGRP）样免疫反应性释放的可能影响。低pH缓冲液（pH 7、6、5）、辣椒素（10⁻⁷ M）、乳酸（5、20、50 mM）和尼古丁（10⁻⁴ M）均能引起明显的CGRP样免疫反应性释放。用辣椒平（10⁻⁶至10⁻⁵ M）孵育可显著降低低pH、辣椒素和乳酸（5 mM）引起的CGRP样免疫反应性释放，但不能降低尼古丁引起的释放。此外，用辣椒平孵育可抑制辣椒素引起的心率刺激。无机染料钌红先前已被证明可减弱辣椒素而非尼古丁诱导的心脏CGRP释放，它也能减少低pH和乳酸（5 mM）引起的CGRP释放。结论是，低pH和乳酸从心脏引起的CGRP样免疫反应性释放与辣椒素引起的释放具有几个共同特征。由于心肌缺血时组织pH较低，且众所周知这会引起疼痛，使用辣椒平抑制C纤维传入神经的功能可能代表一种影响与心脏病理状况相关的自主反射反应的新原理。
