Kinin-B2 receptor mediated neuroprotection after NMDA excitotoxicity is reversed in the presence of kinin-B1 receptor agonists.
Kinin-B2 receptor mediated neuroprotection after NMDA excitotoxicity is reversed in the presence of kinin-B1 receptor agonists.
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DOI：
10.1371/journal.pone.0030755
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ulrich H
中科院分区：
文献类型：
--
作者：
Martins AH;Alves JM;Perez D;Carrasco M;Torres-Rivera W;Eterović VA;Ferchmin PA;Ulrich H
Kinins, with bradykinin and des-Arg9-bradykinin being the most important ones, are pro-inflammatory peptides released after tissue injury including stroke. Although the actions of bradykinin are in general well characterized; it remains controversial whether the effects of bradykinin are beneficial or not. Kinin-B2 receptor activation participates in various physiological processes including hypotension, neurotransmission and neuronal differentiation. The bradykinin metabolite des-Arg9-bradykinin as well as Lys-des-Arg9-bradykinin activates the kinin-B1 receptor known to be expressed under inflammatory conditions. We have investigated the effects of kinin-B1 and B2 receptor activation on N-methyl-D-aspartate (NMDA)-induced excitotoxicity measured as decreased capacity to produce synaptically evoked population spikes in the CA1 area of rat hippocampal slices. Bradykinin at 10 nM and 1 µM concentrations triggered a neuroprotective cascade via kinin-B2 receptor activation which conferred protection against NMDA-induced excitotoxicity. Recovery of population spikes induced by 10 nM bradykinin was completely abolished when the peptide was co-applied with the selective kinin-B2 receptor antagonist HOE-140. Kinin-B2 receptor activation promoted survival of hippocampal neurons via phosphatidylinositol 3-kinase, while MEK/MAPK signaling was not involved in protection against NMDA-evoked excitotoxic effects. However, 100 nM Lys-des-Arg9-bradykinin, a potent kinin-B1 receptor agonist, reversed bradykinin-induced population spike recovery. The inhibition of population spikes recovery was reversed by PD98059, showing that MEK/MAPK was involved in the induction of apoptosis mediated by the B1 receptor. Bradykinin exerted protection against NMDA-induced excitotoxicity which is reversed in the presence of a kinin-B1 receptor agonist. As bradykinin is converted to the kinin-B1 receptor metabolite des-Arg9-bradykinin by carboxypeptidases, present in different areas including in brain, our results provide a mechanism for the neuroprotective effect in vitro despite of the deleterious effect observed in vivo.
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影响因子：
3.3
作者：
Martel, M. -A.;Wyllie, D. J. A.;Hardingham, G. E.
通讯作者：
Hardingham, G. E.
影响因子：
5.3
作者：
Kohno, Tatsuro;Wang, Haibin;Woolf, Clifford J.
通讯作者：
Woolf, Clifford J.
影响因子：
4.2
作者：
Kaplanski, J;Pruneau, D;Shapira, Y
通讯作者：
Shapira, Y
影响因子：
4.8
作者：
Martins, AHB;Resende, RR;Ulrich, H
通讯作者：
Ulrich, H
影响因子：
7.3
作者：
Bellucci, F.;Cucchi, P.;Maggi, C. A.
通讯作者：
Maggi, C. A.