Furthermore, the efficacy of TK was enhanced by pretreatment with the B1R antagonist but was abolished by the B2R antagonist (P < 0.
Compared to TK-treated animals, B1R antagonism prior to MCAO attenuated IL-1[beta] expression, whereas B2R antagonism elevated the levels of IL-1[beta] and TNF-[alpha] (P < 0.
The efficacy of TK treatment was enhanced with the B1R antagonist but reversed with the B2R antagonist (P < 0.
Pretreatment with a B1R antagonist further elevated the levels of p/T-CREB and Bcl-2/[beta]-actin in TK-treated animals (P < 0.
Additionally, the neuroprotective effects of TK were promoted by a B1R antagonist but were abrogated by treatment with a B2R antagonist or ERK1/2 inhibitor.
However, in the present study, blockade of B1R before MCAO facilitated the actions of TK, indicating that activation of B1R exaggerated cerebral I/R injury in diabetic rats.
A previous study on myocardial ischemia demonstrated a cardioprotective effect of the B2R agonist in nondiabetic mice and the B1R agonist in diabetes via inhibition of GSK-3[beta] .
Additionally, pretreatment with the B1R antagonist strengthened the actions of TK on the abovementioned signaling pathways, whereas the B2R antagonist or ERK1/2 inhibitor U0126 produced the opposite effects on these signaling proteins.