Figure 3. Kinin-B2 receptor mediated protection against NMDA-induced excitotoxicity and its reversion by Lys-des-Arg⁹-bradykinin.

Peak areas of synaptically elicited population spikes (PSs) recorded in the stratum pyramidale region of hippocampal slices are reported as mean values ± S.E.M. Bradykinin (BK) (10 nM and 1 µM) protected against NMDA (0.5 mM)-mediated cytotoxicity (n = 21, *** p<0.001, compared to control values in the presence of NMDA alone). Neuroprotection induced by 10 nM BK was abolished in the presence of 100 nM HOE-140 (HOE) (n = 21, ### p<0.001, values obtained in the presence of NMDA and BK compared to those collected in the presence of NMDA, BK and HOE-140). The MEK/MAPK inhibitor PD98059 (50 µM) did not interfere with BK-mediated neuroprotection. The PI3-kinase inhibitor LY294002 (10 µM) co-applied with 10 nM BK blocked neuroprotection conferred by BK (n = 21, p<0.05, compared to control values in the presence of BK alone). BK (10 nM)-exerted effects were abolished by 100 nM of the B1BKR agonist Lys-des-Arg⁹-BK (p<0.001, compared to control values in the presence of BK alone). Lys-des-Arg⁹-BK-mediated blockade of neuroprotection was reverted in the presence of PD98059 (50 µM) or the B1BKR antagonist Lys-des-Arg⁹-Leu⁸-bradykinin (1 µM) (p<0.001, compared to control values in the presence of BK and Lys-des-Arg⁹-BK) (n = 21). Statistical analysis was done by one way ANOVA followed by the Dunn's method.