Mitchell J A, Williams F M, Williams T J, Larkin S W
Department of Applied Pharmacology, National Heart and Lung Institute, London, UK.
Neuropeptides. 1997 Aug;31(4):333-8. doi: 10.1016/s0143-4179(97)90068-8.
Perivascular sensory nerves release calcitonin gene-related peptide (CGRP) and substance P, the dilator actions of which can be regulated by nitric oxide (NO). This study investigated the role of NO in the vasodilation caused by sensory nerve stimulation, by capsaicin, or exogenous CGRP and substance P in the isolated perfused coronary circulation of the rabbit. Coronary perfusion pressure (CPP) was raised in order to observe vasodilator responses, using the thromboxane mimetic, U46619. Capsaicin (3 x 10(-6) moles), alpha CGRP (3 x 10(-11) moles) and substance P (3 x 10(-12) moles) caused comparable reductions in CCP. At these concentrations, responses to capsaicin and CGRP were inhibited by the antagonist CGRP(8-37) but unaffected by the neurokinin-1 receptor antagonist, CP 96,345. The nitric oxide synthase inhibitor, NG nitro L-arginine methyl ester inhibited the effects of substance P and capsaicin but not CGRP. These results suggest that CGRP release following capsaicin-induced sensory nerve activation is modulated by NO.
血管周围感觉神经释放降钙素基因相关肽(CGRP)和P物质,其舒张作用可受一氧化氮(NO)调节。本研究通过在兔离体灌注冠状动脉循环中,研究NO在感觉神经刺激、辣椒素或外源性CGRP和P物质所引起的血管舒张中的作用。使用血栓素类似物U46619升高冠状动脉灌注压(CPP)以观察血管舒张反应。辣椒素(3×10⁻⁶摩尔)、αCGRP(3×10⁻¹¹摩尔)和P物质(3×10⁻¹²摩尔)使CPP产生类似程度的降低。在这些浓度下,辣椒素和CGRP的反应被拮抗剂CGRP(8 - 37)抑制,但不受神经激肽-1受体拮抗剂CP 96,345的影响。一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯抑制P物质和辣椒素的作用,但不抑制CGRP的作用。这些结果表明,辣椒素诱导的感觉神经激活后CGRP的释放受NO调节。