Eurin J, Barthélemy C, Masson F, Soualmia H, Sarfati E, Carayon A
Laboratoire de l'Ecole Pratique des Hautes Etudes, Service de biochimie médicale, CHU Pitié-Salpêtrière, 91, Boulevard de l'hopital, 75013 Paris, France.
Neuropeptides. 2002 Aug;36(4):257-62. doi: 10.1016/s0143-4179(02)00025-2.
Neuropeptide Y (NPY) and noradrenaline (NA) are frequently co-localized and co-released in the sympathetic nervous system. Since bradykinin (BK) is known to stimulate neurotransmitter release as NA in adrenal glands, we therefore hypothesized that BK might also be involved in the release of NPY. The effect of BK(1-9) on immunoreactive NPY (Ir-NPY) release was investigated in superfused human pheochromocytoma tissue. BK(1-9) (10(-7)-10(-5) M) was shown to induce a rapid Ir-NPY release in a concentration-dependent manner. This effect of BK(1-9) (10(-6) M) was mimicked by the B2 agonist [Phe(8)(CH(2)NH)Arg(9)]-bradykinin (10(-5) M) and blocked by the selective B2-receptor antagonist HOE140 (10(-5) M). Increasing Ir-NPY release was probably not mediated by nitric oxide (NO) since the outflow of Ir-NPY was not influenced by the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M). In presence of bapta-AM (10(-5) M), a chelator of cytosolic calcium, W7 (10(-5) M), a calmodulin inhibitor, TMB-8 (10(-5) M), a blocker of intracellular calcium mobilization and ryanodine (10(-5) M), a selective inhibitor of the Ca(2+)-induced release mechanism, the NPY release by BK(1-9) was significantly inhibited by 126%, 98%, 91%, and 94%, respectively. These results indicate that BK increased the release of NPY by the tumor acting through the interaction with the BK-B2 receptor and request intracellular calcium mobilization independently of a NO mechanism.
神经肽Y（NPY）和去甲肾上腺素（NA）在交感神经系统中常共定位并共同释放。由于已知缓激肽（BK）可刺激肾上腺中作为去甲肾上腺素的神经递质释放，因此我们推测BK可能也参与NPY的释放。在灌注的人嗜铬细胞瘤组织中研究了BK（1-9）对免疫反应性NPY（Ir-NPY）释放的影响。结果显示，BK（1-9）（10⁻⁷ - 10⁻⁵ M）以浓度依赖的方式诱导Ir-NPY快速释放。BK（1-9）（10⁻⁶ M）的这种作用被B2激动剂[Phe(8)(CH₂NH)Arg(9)]-缓激肽（10⁻⁵ M）模拟，并被选择性B2受体拮抗剂HOE140（10⁻⁵ M）阻断。Ir-NPY释放增加可能不是由一氧化氮（NO）介导的，因为Ir-NPY的流出不受NO合酶抑制剂N-ω-硝基-L-精氨酸甲酯（L-NAME）（10⁻⁴ M）的影响。在存在胞质钙螯合剂bapta-AM（10⁻⁵ M）、钙调蛋白抑制剂W7（10⁻⁵ M）、细胞内钙动员阻滞剂TMB-8（10⁻⁵ M）和Ca²⁺诱导释放机制的选择性抑制剂ryanodine（10⁻⁵ M）的情况下，BK（1-9）引起的NPY释放分别被显著抑制了126%、98%、91%和94%。这些结果表明，BK通过与BK-B2受体相互作用增加肿瘤中NPY的释放，且需要细胞内钙动员，与NO机制无关。
