Källner G, Franco-Cereceda A
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
Eur J Pharmacol. 1998 Jul 10;352(2-3):223-8. doi: 10.1016/s0014-2999(98)00348-3.
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.
本研究旨在以钙通道依赖性、与ATP敏感性钾通道(K(ATP)通道)的相互作用以及动作电位传播的作用为依据,在离体灌注豚鼠心脏中,对辣椒素、低pH值和前列环素引起的降钙素基因相关肽(CGRP)释放进行特征描述。钙通道阻滞剂ω-芋螺毒素降低了10⁻⁷ M辣椒素诱发的CGRP释放以及pH 7诱发的CGRP释放。低浓度(10⁻⁷ M)而非高浓度(10⁻⁶ M)辣椒素引起的CGRP释放也因河豚毒素而减弱,表明部分依赖动作电位传播。前列环素引起的CGRP释放不受任何一种受试药物的影响。ATP敏感性钾通道激活剂克罗卡林和ATP敏感性钾通道阻滞剂格列本脲对CGRP释放无影响。因此,先前的研究结果得到支持,即低pH值和辣椒素至少部分通过共同机制刺激离体心脏中对辣椒素敏感的传入神经。河豚毒素减弱辣椒素诱发的CGRP释放表明通过局部轴突反射募集了额外的神经末梢。