Binding capacity of FK506 binding protein after 2-hour hemispheric ischemia in gerbil brain.
The binding capacity of FK506 binding protein (FKBP) was examined after 2-h hemispheric ischemia in the gerbil brain in order to clarify the precise mechanism of the neuroprotective effects of FK506. Firstly, the FK506 binding was evaluated in vitro in the normal gerbil brain using 1 nM [3H]dihydro-FK506 as a specific ligand. FK506 binding sites were 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 divided into two groups: an ischemia group (n = 12) and a sham group (n = 6). The right common carotid artery was ligated to induce hemispheric ischemia for 2 h in the ischemia group. The local cerebral blood flow was measured at the end of the experiment by the [14C]iodoantipyrine method. The ligated animals with levels of local cerebral blood flow in the lateral nuclei of the thalamus of less than 50 ml/100 g/min were utilized as the ischemia group (n=6) for further data analysis. No significant differences in FK506 binding between the ischemia and sham groups were observed in any regions. The above data indicate that the binding capacity of FKBP tends to remain normal during 2-h ischemia, suggesting that FK506 may exert its neuroprotective effects through its binding to FKBP in the brain during the early phase of cerebral ischemia.
Nozaki
H
H
Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan. hiroyuki_nozaki@msn.com
Tanaka
K
K
Shirai
T
T
Nagata
E
E
Kondo
T
T
Koyama
S
S
Dembo
T
T
Fukuuchi
Y
Y
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005849:Gerbillinae; D006360:Heat-Shock Proteins / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D022021:Tacrolimus Binding Proteins