Intravenously injected FK506 failed to inhibit hippocampal calcineurin

FK506 (tacrolimus) is known as an inhibitor for calcineurin and is used in numerous research fields. It is not clear whether intravenously injected FK 506 inhibits neuronal calcineurin. We measured the calcineurin activities o f normal and postischemic rat hippocampi after intravenous injection of FK5 06 (3 mg/kg). Intravenously injected FK506 had no inhibitory effect on calc ineurin activity in the hippocampi of normal and postischemic rats, whereas FK506 inhibited the calcineurin in vitro (purified enzyme, hippocampal hom ogenate, and hippocampal slice culture homogenate). Thus, it is considered that intravenously injected FK506 does not act on intraneuronal calcineurin and that several effects of FK506 are not due to the inhibition of neurona l calcineurin. (C) 2001 Academic Press.