Abstract
The blood–brain barrier (BBB) plays a crucial regulatory role in central nervous system (CNS) function and in communication between the CNS and the periphery. In addition to lipophilic molecules, many small proteins are now known to cross the BBB. Such recognition was expedited by techniques that quantify the influx and efflux of peptides and polypeptides across the BBB of the living animal. These methods are described in this review. Their use has enhanced our knowledge of the crucial link between the CNS and the rest of the body, and this has physiological and pathological implications as well as therapeutic potential.
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References
Oldendorf, W. Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. Am. J. Physiol., 1971; 221: 16929–16939.
Rapoport, S.I. Blood-Brain Barrier in Physiology and Medicine. Raven Press, New York, 1976.
Davson, H., and Segal, M.B. Physiology of the CSF and Blood–Brain Barriers. CRC Press, Boca Raton, FL, 1996.
Begley, D.J. Peptides and the blood-brain barrier. In Handbook of Experimental Pharmacology, Physiology and Pharmacology of the Blood–Brain Barrier, Vol. 103, M.W.B. Bradbury, ed. Springler-Verlag, Berlin, 1992, pp. 151–203.
Kastin, A.J., Hahn, K., and Zadina, J.E. Regional differences in peptide degradation by rat cerebral microvessels: A novel regulatory mechanism for communication between blood and brain. Life Sci., 2001; 69: 1305–1312.
Fenstermacher, J.D. Methods for quantifying the transport of drugs across blood–brain barrier systems. Pharmacol. Ther., 1981; 14: 217–248.
Blasberg, R.G., Fenstermacher, J.D., and Patlak, C.S. Transport of à-aminoisobutyric acid across brain capillary and cellular membranes. J. Cereb. Blood Flow Metab., 1983; 3: 8–22.
Patlak, C.S., Blasberg, R.G., and Fenstermacher, J.D. Graphical evaluation of blood-to-brain transfer constants from multiple time uptake data. J. Cereb. Blood Flow Metab., 1983; 3: 1–7.
Kastin, A.J., Nissen, C., and Coy, D.H. Permeability of the blood–brain barrier to DSIP peptides. Pharmacol. Biochem. Behav., 1981; 15: 955–959.
Banks, W.A., Jaspan, J.B., and Kastin, A.J. Selective, physiological transport of insulin across the blood-brain barrier: Novel demonstration by species-specific radioimmunoassays. Peptides, 1997; 18: 1257–1262.
Hunter, W.M., and Greenwood, F.C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature, 1962; 194: 495–496.
Marchalonis, J. An enzymic method for the trace iodination of immunoglobulins and other proteins. Biochem. J., 1969; 113: 299–305.
Bolton, A.E., and Hunter, W.M. A new method for labelling protein hormones with radioiodine for use in the radioimmunoassay. J. Endocrinol., 1972; 55: xxx–xxxi.
O’Rourke. E.C., Drummond, R.J., and Creasey, A.A. Binding of 125I-labeled recombinant βinterferon (IFN-β Ser17) to human cells. Mol. Cell. Biol., 2006; 4: 2745–2749.
Banks, W.A., and Kastin, A.J.. Opposite direction of transport across the blood–brain barrier for Tyr-MIF-1 and MIF-1: Comparison with morphine. Peptides, 1994; 15: 23–29.
Kastin, A.J., Akerstrom, V., and Pan, W. Validity of multiple-time regression analysis in measurement of tritiated and iodinated leptin crossing the blood–brain barrier: Meaningful controls. Peptides, 2001; 22: 2127–2136.
Banks, W.A., and Kastin, A.J. Peptides and the blood–brain barrier: Lipophilicity as a predictor of permeability. Brain Res. Bull., 1985; 15: 287–292.
Chikhale, E.G., Ng, K.Y., Burton, P.S., and Borchardt, R.T. Hydrogen bonding potential as a determinant of the in vitro and in situ blood–brain barrier permeability of peptides. Pharm. Res., 1994; 11: 412–419.
Egleton, R.D., and Davis, T.P. Bioavailability and transport of peptides and peptide drugs into the brain. Peptides, 1997; 18: 1431–1439.
Kastin, A.J., Pan, W., Maness, L.M., and Banks, W.A. Peptides crossing the blood–brain barrier: Some unusual observations. Brain Res., 1999; 848: 96–100.
Pan, W., Banks, W.A., and Kastin, A.J. Permeability of the blood–brain and blood-spinal cord barriers to interferons. J. Neuroimmunol., 1997; 76: 105–111.
Banks, W.A., and Kastin, A.J. Differential permeability of the blood–brain barrier to two pancreatic peptides: Insulin and amylin. Peptides, 1998; 19: 883–889.
Nonaka, N., Banks, W.A., Mizushima, H., Shioda, S., and Morley, J.E. Regional differences in PACAP transport across the blood-brain barrier in mice: A possible influence of strain, amyloid beta protein, and age. Peptides, 2002; 12: 2197–2202.
Pan, W., Ding, Y., Yu, Y., Ohtaki, H., Nakamichi, T., and Kastin, A.J. Stroke upregulates TNF alpha transport across the blood–brain barrier. Exp. Neurol., 2006; 198: 222–233.
Kastin, A.J., and Pan, W. Editorial: Intranasal leptin: Blood–brain barrier bypass (BBBB) for obesity? Endocrinology, 2006; 147: 2086–2087.
Johanson, C.E. The choroid plexus–CNF nexus. In Neuroscience in Medicine, P.M. Conn, ed. Humana Press Inc., Totawa, Press, 2003, pp. 165–195.
Plotkin, S.R., Banks, W.A., and Kastin, A.J. Comparison of saturable transport and extracellular pathways in the passage of interleukin-1 à across the blood–brain barrier. J. Neuroimmunol., 1996; 67: 41–47.
Maness, L.M., Kastin, A.J., and Banks, W.A. Relative contributions of a CVO and the microvascular bed to delivery of blood-borne IL-1à to the brain. Am. J. Physiol., 1998; 275: E207–E212.
Triguero. D., Buciak, J., and Pardridge, W.M. Capillary depletion method for quantification of blood–brain barrier transport of circulating peptides and plasma proteins. J. Neurochem., 1990; 54: 1882–1888.
Gutierrez, E.G., Banks, W.A., and Kastin, A.J. Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J. Neuroimmunol., 1993; 47: 169–176.
Pan, W., Vallance, K.L., and Kastin, A.J. TGF alpha and the blood–brain barrier: Accumulation in cerebral vasculature. Exp. Neurol., 1999; 160: 454–459.
Yu, C., Kastin, A.J., Ding, Y., and Pan, W. Gamma glutamyl transpeptidase is a dynamic indicator of endothelial response to stroke. Exp. Neurol., 2007; 203: 116–122.
Hoke, F. Recent advances increase HPLC use in life sciences. Scientist, 1993; 7: 18–19.
Fischman, A.J., Kastin, A.J., and Graf, M.V. HPLC shadowing: Artifacts in peptide characterization monitored by RIA. Peptides, 1984; 5: 1007–1010.
Crone, C. The permeability of capillaries of various organs as determined by the use of the “indicator diffusion” method. Acta Physiol. Scand., 1963; 58: 292–305.
Olendorf, W.H. Measurement of brain uptake of radiolabeled substances using a tritiated water internal standard. Brain Res., 1970; 24: 372–376.
Kastin, A.J., Pan, W. Piptide transport across the blood-brain barrier. In Prokai, L., Prokai-Tatrai, K. eds. Piptide Transport and Delivery into the Central Nervous System, pp. 79–100. Basel, Switzerland: Birkhauser Verlag, 2003.
Pan, W., Kastin, A.J. Why study transport of peptides and proteins at the neurovascular interface. Brain Res. Rev., 2004; 46: 32–43.
Maness, L.M., Kastin, A.J., Farrell, C.L., and Banks, W.A. Fate of leptin after intracerebroventricular injection into the mouse brain. Endocrinology, 1998; 139(11): 4556–4562.
Banks, W.A., and Kastin, A.J. Quantifying carrier-mediated transport of peptides from the brain to the blood. In Methods in Enzymology, Vol. 168, P.M. Conn, ed. Academic Press, San Diego, 1998; pp. 652–660.
Banks, W.A., Kastin, A.J., Horvath, A., and Michals, E.A. Carrier-mediated transport of vasopressin across the blood-brain barrier of the mouse. J. Neurosci. Res., 1987; 18: 326–332.
Kastin, A.J., Banks, W.A., Hahn, K., and Zadina, J.E. Extreme stability of Tyr-MIF-1 in CSF. Neurosci. Lett., 1994; 174: 26–28.
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Pan, W., Kastin, A. (2008). In vivo Techniques Quantifying Blood-Brain Barrier Permeability to Small Proteins in Mice. In: Gozes, I. (eds) Neuropeptide Techniques. Neuromethods, vol 39. Humana Press. https://doi.org/10.1007/978-1-60327-099-1_8
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DOI: https://doi.org/10.1007/978-1-60327-099-1_8
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