Saturable entry of ciliary neurotrophic factor into brain.
Ciliary neurotrophic factor (CNTF), like tumor necrosis factor-alpha (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), is a cytokine with neurotrophic properties. Since all three cytokines are found in the periphery as well as brain, and since TNF and GM-CSF cross the blood-brain barrier (BBB) by a saturable mechanism, we investigated whether CNTF also saturably enters the brain from the blood. We found that CNTF crosses the BBB rapidly, with a rate of entry (Ki) of 4.60 (+/-0.78) x 10(-4) ml/g min, considerably faster than that of the 99mTc-albumin control. The Ki was reduced more than 3-fold by addition of excess unlabeled CNTF. The results indicate that CNTF is saturably transported across the BBB from blood to brain.
Pan
W
W
Department of Medicine, VA Medical Center and Tulane University School of Medicine, New Orleans, LA 70112-1262, USA. wpan@mailhost.tcs.tulane.edu
Kastin
A J
AJ
Maness
L M
LM
Brennan
J M
JM
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D020934:Ciliary Neurotrophic Factor; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012044:Regression Analysis; D013668:Technetium Tc 99m Aggregated Albumin / Q000493:pharmacokinetics
D020934:Ciliary Neurotrophic Factor; D007457:Iodine Radioisotopes; D009419:Nerve Tissue Proteins; D013668:Technetium Tc 99m Aggregated Albumin