Summary
1. Four parts of human brain were extracted by successive ammonium sulphate and acetic acid-ether precipitations. The resulting extracts contained substance P but were found to be free of other substances which are known to influence capillary permeability (acetyl choline, adrenergic amines, histamine, serotonin, ATP, ADP, AMP).
2. The extracts were tested for substance P activity on the guinea pig's ileum and for activity in increasing capillary permeability on the rabbit's skin. The substance P content was found to be 719 units/g in substancia nigra, 120 units/g in basal ganglia, 34 units/g in cortex, < 2 units/g in cerebellum. Equal increase in capillary permeability was produced by extracts corresponding to 40–50 mg of substancia nigra, 200–300 mg of basal ganglia, 300–400 mg of cortex, 600–800 mg of cerebellum. This shows a close relation between substance P content and effectiveness in increasing capillary permeability in four parts of brain.
3. Since extracts of these four parts with equal activity in increasing permeability contained different amounts of substance P, other material capable of increasing capillary permeability must be present. This becomes appearent especially when larger quantities of the extracts had to be injected. By means of paper chromatography a separation could be achieved in intestinal but not in brain extracts.
4. It seems to be possible that substance P enables those parts of the brain which are rich in it to have particularly high rates of exchange, either potential or permanent, between the capillaries and the surrounding tissue.
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Literatur
Amin, A. H., T. B. B. Crawford, and J. H. Gaddum: The distribution of substance P and 5-hydroxytryptamine in the central nervous system of the dog. J. Physiol. (Lond.) 126, 596 (1954).
Anton, A. H., and D. F. Sayre: A study of the factors affecting the aluminium oxide-trihydroxyindole procedure for the analysis of catecholamines. J. Pharmacol. exp. Ther. 138, 360 (1962).
Bisset, G. W., and G. P. Lewis: A spectrum of pharmacological activity in some biologically active peptides. Brit. J. Pharmacol. 19, 168 (1962).
Boissonnas, R. A., J. Franz, and E. Stürmer: On the chemical characterization of substance P. Ann. N.Y. Acad. Sci. 104, 376 (1963).
Burckhardt, D.: Beeinflußbarkeit der durch Polypeptide erhöhten Kapillarpermeabilität bei Meerschweinchen und Ratten. Helv. physiol. pharmacol. Acta 20, 135 (1962).
Collier, H. O. J., and I. R. Lee: Nociceptive responses of guinea-pigs to intradermal injections of bradykinin and kallidin-10. Brit. J. Pharmacol. 21, 155 (1963).
Eber, O., u. F. Lembeck: Über den enzymatischen Abbau der Substanz P. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 229, 139 (1956).
Feldberg, W.: Distribution of histamine in the body. In: Ciba Foundation Symposium on Histamine. London: Churchill Ltd. 1956.
Fleckenstein, A., u. E. Gerlach: Papierchromatographische Trennung von Adenosintriphosphat, Adenosindiphosphat und anderen Phosphorverbindungen bei Säugetier- und Tauben-Erythrocyten verschiedenen K+-Gehalts. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 219, 531 (1953).
Franz, J., R. A. Boissonnas u. E. Stürmer: Isolierung von Substanz P aus Pferdedarm und ihre biologische und chemische Abgrenzung gegenüber Bradykinin. Helv. chim. Acta 44, 881 (1961).
Frimmer, M., u. F. W. Müller: Brauchbarkeit und Grenzen der Farbstoffmethoden zur Bestimmung vermehrter Durchlässigkeit der Haut-Capillaren. Med. exp. (Basel) 6, 327 (1962).
Hais, I. M., u. K. Macek: Handbuch der Papierchromatographie, Bd. I: Grundlagen und Technik. Jena: G. Fischer 1958.
Hanes, C. S., and F. A. Isherwood: Separation of the phosphoric esters on the filter paper chromatogram. Nature (Lond.) 164, 1107 (1949).
Hellauer, H.: Zur Charakterisierung der Erregungssubstanz sensibler Nerven. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 219, 234 (1953).
K. Umrath: The transmitter substance of sensory nerve fibres. J. Physiol. (Lond.) 106, 20P (1947).
Jaques, R.: Diskussionsbemerkung. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 245, 276 (1963).
Judah, J. D., and D. A. Willoughby: A quantitative method for the study of capillary permeability: Extraction and determination of trypan blue in tissues. J. Path. Bact. 83, 567 (1962).
Lembeck, F.: Zur Frage der zentralen Übertragung afferenter Impulse. III. Mitteilung. Das Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Rückenmarks. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 219, 197 (1953).
—: Über den Nachweis von 5-Oxytryptamin (Enteramin, Serotonin) in Carcinoidmetastasen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 221, 50 (1954).
—, and K. Starke: Substance P content and effect on capillary permeability of extract of various parts of human brain. Nature (Lond.) 199, 1295 (1963).
—, and G. Zetler: Substance P: a polypeptide of possible physiological significance, especially within the nervous system. Int. Rev. Neurobiol. 4, 159 (1962).
Miles, A. A., and E. M. Miles: Vascular reactions to histamine, histamine-liberator and leukotaxine in the skin of guinea-pigs. J. Physiol. (Lond.) 118, 228 (1952).
—, and D. L. Wilhelm: Enzyme-like globulins from serum reproducing the vascular phenomena of inflammation. I. An activable permeability factor and its inhibitor in guinea-pig serum. Brit. J. exp. Path. 36, 71 (1955).
Partridge, S. M.: Filter paper partition chromatography of sugars. I. General discription and application to the qualitative analysis of sugars in apple juice, egg white and fetal blood of sheep. Biochem. J. 42, 238 (1948).
Pernow, B.: Studies on Substance P. Acta physiol. scand. 29, Suppl. 105, 1 (1953).
Rawson, R. A.: The binding of T-1824 and structurally related diazo dyes by the plasma proteins. Amer. J. Physiol. 138, 708 (1943).
Shipley, R. E., and J. H. Tilden: A pithed rat preparation suitable for assaying pressor substances. Proc. Soc. exp. Biol. (N.Y.) 64, 453 (1947).
Sparrow, E. M., and D. L. Wilhelm: Species differences in susceptibility to capillary permeability factors: histamine, 5-hydroxytryptamine and compound 48/80. J. Physiol. (Lond.) 137, 51 (1957).
Spector, W. G.: Substances which affect capillary permeability. Pharmacol. Rev. 10, 475 (1958).
Toh, C. C.: Biologically active substances in brain extracts. J. Physiol. (Lond.) 165, 47 (1963).
Udenfriend, S.: Fluorescence Assay in Biology and Medicine. New York, London: Academic Press 1962.
Umrath, K.: Über die fermentative Verwandlung von Substanz P aus sensiblen Neuronen in die Erregungssubstanz der sensiblen Nerven. Pflügers Arch. ges. Physiol. 258, 230 (1953).
Vogler, K., W. Haefely, A. Hürlimann, R. O. Studer, W. Lergier, R. Strässle, and K. H. Berneis: A new purification procedure and biological properties of substance P. Ann. N.Y. Acad. Sci. 104, 378 (1963).
Weber, E.: Grundriß der biologischen Statistik. 4. Aufl. Jena: G. Fischer 1961.
Weil-Malherbe, H., J. Axelrod, and R. Tomchick: Blood-brain-barrier for adrenaline. Science 129, 1226 (1959).
Wells, A. Q., D. M. Oxon, and E. A. Carmichael: Microglia: an experimental study by means of tissue culture and vital staining. Brain 53, 1 (1930).
Whittaker, V. P.: Pharmacological studies with isolated cell components. Biochem. Pharmacol. 9, 61 (1962).
Wilhelm, D. L.: The mediation of increased vascular permeability in inflammation. Pharmacol. Rev. 14, 251 (1962).
Wilson, C. W. M., and B. B. Brodie: The absence of blood-brain-barrier from certain areas of the central nervous system. J. Pharmacol. 133, 332 (1961).
Wislocki, G. B., and L. S. King: The permeability of the hypophysis and hypothalamus to vital dyes, with a study of the hypophyseal vascular supply. Amer. J. Anat. 58, 421 (1936).
—, and E. H. Leduc: Vital staining of the hematoencephalic barrier by silver nitrate and trypan blue, and cytological comparisons of the neurohypophysis, pineal body, area postrema, intercolumnar tubercle and supraoptic crest. J. comp. Neurol. 96, 371 (1952).
Zetler, G., u. L. Schlosser: Über die Verteilung von Substanz P und Cholinacetylase im Gehirn. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 224, 159 (1955).
Zuber, H.: Isolation of substance P from bovine brain. Ann. N.Y. Acad. Sci. 104, 391 (1963).
—, u. R. Jaques: Isolierung von Substanz P aus Rinderhirn. Angew. Chem. 74, 216 (1962).
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Starke, K. Substanz P-Gehalt und permeabilitätserhöhende Wirkung in verschiedenen Gehirngebieten. Naunyn - Schmiedebergs Arch 247, 149–163 (1964). https://doi.org/10.1007/BF00245418
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DOI: https://doi.org/10.1007/BF00245418