BINDING-CAPACITY OF FK506 BINDING-PROTEIN AFTER 2-HOUR HEMISPHERIC ISCHEMIA IN GERBIL BRAIN

The binding capacity of FK506 binding protein (FKBP) was examined afte r 2-h hemispheric ischemia in the gerbil brain in order to clarify the precise mechanism of the neuroprotective effects of FK506. Firstly, t he FK506 binding was evaluated in vitro in the normal gerbil brain usi ng 1 nM [H-3]dihydro-FK506 as a specific ligand. FK506 binding sites w ere distributed in a rather homogeneous manner, although the greatest binding was noted in the hippocampus CA1. Secondly, Scatchard analysis demonstrated that the binding sites of FK506 could be composed of two components in each brain region. Thirdly, 18 Mongolian gerbils were d ivided into two groups: an ischemia group (n = 12) and a sham group (n = 6). The right common carotid artery was ligated to induce hemispher ic ischemia for 2 h in the ischemia group. The local cerebral blood fl ow was measured at the end of the experiment by the [C-14]iodoantipyri ne method. The ligated animals with levels of local cerebral blood flo w in the lateral nuclei of the thalamus of less than 50 ml/100 g/min w ere utilized as the ischemia group (n = 6) for further data analysis. No significant differences in FK506 binding between the ischemia and s ham groups were observed in any regions. The above data indicate that the binding capacity of FKBP tends to remain normal during 2-h ischemi a, suggesting that FK506 may exert its neuroprotective effects through its binding to FKBP in the brain during the early phase of cerebral i schemia. (C) 1998 Elsevier Science B.V.