Bellido L, López-González M A, Pedrera C, Lucas M
Departamento de Bioquímica Médica y Biolgía Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina, Sevilla, Spain.
Life Sci. 1994;54(24):1909-16. doi: 10.1016/0024-3205(94)90149-x.
N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) induced in lymphocytes the production of reactive oxygen intermediates in a process which was inhibited by the presence of Vasoactive Intestinal Peptide (VIP) in a dose-dependent response at VIP concentrations in the range 10(-10)-10(-7) M. The dissociation constant for the high-affinity receptors of VIP agrees with the ID50 of the activation of adenylate cyclase which are close to 0.2 nM VIP, whereas the ID50 for the inhibition by VIP of fMLP-induced chemiluminescence approaches to 5 nM VIP. Both IBMX and Forskolin produced in lymphocytes an inhibition of fMLP-induced chemiluminescence. The degree of inhibition was ascertained to be additive in the presence of the above indicated agents and suboptimal concentrations of VIP. The saturation by cAMP of its putative target, the regulatory subunit of protein kinase A, appears to be required for the onset of the inhibitory effect of VIP. This study provides evidence of the molecular signal, namely cAMP, which provokes an inhibitory effect on chemoatractant-stimulated human lymphocytes and further support a role for VIP as a mediator in the neuroimmune system.
N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）在淋巴细胞中诱导活性氧中间体的产生，在此过程中，血管活性肠肽（VIP）的存在以剂量依赖性方式抑制该过程，VIP浓度范围为10^(-10)-10^(-7)M。VIP高亲和力受体的解离常数与腺苷酸环化酶激活的半数抑制浓度（ID50）一致，接近0.2 nM VIP，而VIP对fMLP诱导的化学发光抑制的ID50接近5 nM VIP。异丁基甲基黄嘌呤（IBMX）和福斯高林均在淋巴细胞中抑制fMLP诱导的化学发光。在上述试剂和次优浓度的VIP存在下，抑制程度被确定为具有加和性。cAMP对其假定靶点蛋白激酶A调节亚基的饱和似乎是VIP产生抑制作用所必需的。本研究提供了分子信号即cAMP的证据，其对趋化因子刺激的人淋巴细胞产生抑制作用，并进一步支持VIP作为神经免疫系统中介物的作用。
