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Enhanced vesicular transport of exogenous peroxidase across cerebral vessels, induced by serotonin

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Summary

Previous studies have revealed that the endothelial cells of cerebral vessels are linked by tight junctions preventing an intercellular passage of exogenous peroxidase. However, under normal conditions, vesicular transport of the tracer has been demonstrated in parts of cerebral vessels, especially in arterioles with a diamater of 30–100μ. Solutions, containing 50–800 μg of buffered 5-hydroxytryptamine sulphate (serotonin), were perfused through the cerebral ventricles on mice after intravenous injection of horseradish peroxidase. Usually, the biogenic amine enhanced the vesicular transport of exogenous peroxidase. The serotonin-induced increased transport was observed in vessels on the surface of the brain as well as in vessels located in the parenchyma. No cell damage was observed. Increased transport was observed in arterioles, venules, and in capillaries. Therefore, it is not likely that the serotonin effect in a constriction of smooth muscle cells causing an opening of the tight junctions followed by an intercellular movement of tracer. The most reasonable assumption behind the mechanism is that serotonin affects the plasmamembrane of endothelial cells resulting in an enhanced production and transfer of cytoplasmic vesicles.

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References

  • Aghajnian, G. K., Bloom, F. E., Lovell, R. A., Sheard, M. H., Fredeman, D. X.: The uptake of 5-hydroxytryptamine-3H from the cerebral ventricles: autoradiographic localization. Biochem. Pharmacol.15, 1401–1403 (1966)

    Google Scholar 

  • Bertler, Å., Falck, B., Rosengren, E.: The direct demonstration of a barrier mechanism in the brain capillaries. Acta pharmacol. (Kbh.)20, 317–321 (1963)

    Google Scholar 

  • Brightman, M. W., Klatzo, I., Olsson, Y., Reese, T. S.: The blood-brain barrier to proteins under normal and pathological conditions. J. neurol. Sci.10, 215–239 (1970)

    Google Scholar 

  • Brightman, M. W., Reese, T. S.: Junctions between intimately apposed cell membranes in the vertebrate brain. J. Cell Biol.40, 648–677 (1969)

    Google Scholar 

  • Brightman, M. W., Reese, T. S., Feder, N.: Assessment with the electronmicroscope of the permeability of peroxidase of cerebral endothelium and epithelium in mice and sharks. In Capillary permeability. Alfr. Benzon Symp. II, pp. 468–476. Copenhagen: Munksgaard 1970

    Google Scholar 

  • Bulat, M., Supek, Z.: The penetration of 5-hydroxytryptamine through the blood-brain barrier. J. Neurochem.14, 265–271 (1967)

    Google Scholar 

  • Bulat, M., Supek, Z.: Mechanism of 5-hydroxytryptamine penetration through the cerebrospinal fluid-brain barrier. Nature (Lond.)219, 72–73 (1968)

    Google Scholar 

  • Bulle, P. H.: Effects of reserpine and chlorpromazine in prevention of cerebral edema and reversible cell damage. Proc. Soc. exp. Biol. (N. Y.)94, 553–556 (1957)

    Google Scholar 

  • Clasen, R. A., Pandolfi, S., Hass, G. M.: Vital staining, serum albumin and the blood-brain barrier. J. Neuropath. exp. Neurol.29, 266–284 (1970)

    Google Scholar 

  • Costa, J. L., Ito, U., Spatz, M., Klatzo, I., Demirjian, C.: 5-hydroxytryptamine accumulation in cerebrovascular injury. Nature (Lond.)248, 135–136 (1974)

    Google Scholar 

  • Costa, J. L., Ito, U., Spatz, M., Klatzo, I.: Platelets as mediators of CNS damage in cold edema. Abstract, p. 329, Third annual meeting. Society for Neuroscience. San Diego, California (1973)

    Google Scholar 

  • Costa, J., Ito, U., Spatz, M., Klatzo, I.: Observations on endogenous brain monoamine levels in edema and ischemia. J. Neuropath. exp. Neurol. (in press)

  • Cox, J. P., Karnovsky, M. L.: The depression of phagocytosis by exogenous cyclic nucleotides, prostaglandins, and theophylline. J. Cell Biol.59, 480–490 (1973)

    Google Scholar 

  • Deshmukh, V. D., Harper, A. M.: The effect of serotonin on cerebral and extracerebral blood flow with possible implications in magraine. Acta neurol. scand.49, 649–658 (1973)

    Google Scholar 

  • Ehrlich, P.: Zur therapeutischen Bedeutung der substituierende Schwefelsäuregruppe. Ther. Mh.1, 88–90 (1887)

    Google Scholar 

  • Graham, R. C., Karnovsky, J. M.: The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J. Histochem. Cytochem.14, 291–302 (1966)

    Google Scholar 

  • Klatzo, I., Miquel, J., Otenasek, R.: The application of fluorescein labeled serum proteins (FLSP) to the study of vascular permeability in the brain. Acta neuropath. (Berl.)2, 144–160 (1962)

    Google Scholar 

  • Kowalsky, K., Babiarz, D., Buke, G.: Phagocytosis of latex beads by isolated thyroid cells: Effects of thyrotropin, prostaglandin E1 and dibutyryl cyclic AMP. J. Lab. Clin. Med.79, 258–266 (1972)

    Google Scholar 

  • Loizou, L. A.: Uptake of monoamine into central neurones and the blood-brain barrier in the infant rat. Br. J. Pharmac.40, 800–813 (1970)

    Google Scholar 

  • Masur, S. K., Holtzman, E., Walter, R.: Induction of pinocytosis in toad urinary bladder by neurohyophyseal hormone and cyclic AMP. J. Cell Biol.47, 131a-132a (1970)

    Google Scholar 

  • Nørtved, J., Westergaard, E.: Transport of horseradish peroxidase across cerebral arterioles and venules. Anat. Rec.178, 428 (1974)

    Google Scholar 

  • Osterholm, J. L., Bell, J., Meyer, R., Pyenson, J.: Experimental effects of free serotonin on the brain and its relation to brain injury. Part 1: The neurological consequences of intracerebral serotonin injections. Part 2: Trauma-induced alterations in spinal fluid and brain. Part 3. Serotonin-induced cerebral edema. J. Neurosurg.31, 408–421 (1969)

    Google Scholar 

  • Palmer, G. C., Schmidt, M. J., Robinson, G. A.: Development and characteristics of the histamine-induced accumulation of cyclic AMP in the rabbit cerebral cortex. J. Neurochem.19, 2251–2256 (1972)

    Google Scholar 

  • Rechardt, L., Härkönen, M.: Electron microscopic demonstration of adenyl cyclase activity in the nervous tissue. J. Ultrastruct. Res. (in press)

  • Reese, T. S., Feder, N., Brightman, M. W.: Electron microscopic study of the blood-brain and blood-cerebrospinal fluid barriers with microperoxidase. J. Neuropath. exp. Neurol.30, 137–138 (1971)

    Google Scholar 

  • Reese, T. S., Karnovsky, M. J.: Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol.34, 207–217 (1967)

    Google Scholar 

  • Reynolds, E. S.: The use of lead citrate at high pH as an electronopaque stain in electron microscopy. J. Cell Biol.17, 208–212 (1963)

    Google Scholar 

  • Richardson, K. C.: The fine structures of autonomic nerve endings in smooth muscle of the rat vas deferens. J. Anat., Lond.96, 427–442 (1962)

    Google Scholar 

  • Rosendorff, C., Cranston, W. I.: Effects of intrahypothalamic and intraventricular norepinephrine and 5-hydroxytryptamine on hypothalamic blood flow in the conscious rabbit. Circulation Res.28, 492–502 (1971)

    Google Scholar 

  • Schaltenbrand, G., Putnam, T.: Untersuchungen zum Kreislauf des Liquor Cerebrospinalis mit Hilfe intravenöser Fluoresceineinspritzungen. Deutsch. Zeitschr. Nervenheilkunde.96, 123–132 (1927)

    Google Scholar 

  • Schultz, J., Daly, J. W.: Adenosine 3′,5′-monophosphate in guinea pig cerebral cortical slices: effects of α- and β-adrenergic agents, histamine, serotonin and adenosine. J. Neurochem.21, 573–579 (1973a)

    Google Scholar 

  • Schultz, J., Daly, J. W.: Accumulation of cyclic adenosine 3′,5′-monophosphate in cerebral cortical slices from rat and mouse: stimulatory effect of α- and β-adrebergic agents and adenosine. J. Neurochem.21, 1319–1326 (1973b)

    Google Scholar 

  • Seyberth, H. W., Schmidt-Gayk, H., Jakobs, K. H., Hackenthal, E.: Cyclic adenosine monophosphate in phagocytizing granulocytes and alveolar macrophages. J. Cell. Biol.57, 567–571 (1973)

    Google Scholar 

  • Spector, S.: Monoamine oxidase in control of brain serotonin and norepinephrine content. Ann. N.Y. Acad. Sci.120, 856–864 (1963)

    Google Scholar 

  • Spurr, A. R.: A low-viscosity epoxy resin embedding medium for electron microscopy. J. Ultrastruct. Res.26, 31–43 (1969)

    Google Scholar 

  • Swank, R. L., Hissen, W.: Influence of serotonin on cerebral circulation. Arch. Neurol. (Chic.)10, 468–472 (1964)

    Google Scholar 

  • Toda, N., Fujita, Y.: Responsiveness of isolated cerebral and peripheral arteries to serotonin, norepinephrine and transmural electrical stimulation. Circulat. Res.33, 98–104 (1973)

    Google Scholar 

  • Tschirgi, R. D.: Protein complexes and the impermeability of the blood-brain barrier to dyes. Amer. J. Physiol.163, 756 (1950)

    Google Scholar 

  • Welch, K. M. A., Hashi, K., Meyer, J. S.: Cerebrovascular response to intracarotid injection of serotonin before and after middle cerebral artery occlusion. J. Neurol. Neurosurg. Psychiat.36, 724–735 (1973)

    Google Scholar 

  • Welch, K. M. A., Meyer, J. S., Kwant, S.: Estimation of levels of serotonin and 5-hydroxy-indoles in whole blood by an autoanalytical procedure: observations on the blood-brain barrier. J. Neurochem.17, 1079–1087 (1972)

    Google Scholar 

  • Welch, K. M. A., Meyer, J. S., Teraura, T., Hashi, K., Shinmaru, S.: Ischemic anoxia and cerebral serotonin levels. J. neurol. Sci.16, 85–92 (1972)

    Google Scholar 

  • Westergaard, E.: Transport of protein tracers across cerebral arterioles under normal conditions. In: Pathology of cerebral microcirculation. J. Cervos-Navarro (Ed.) pp. 218–227. Berlin-New York: W. de Gruyter & Co. 1974a

    Google Scholar 

  • Westergaard, E.: The effect of serotonin, norepinephrine, and cyclic AMP on the blood-brain barrier. J. Ultrastruct. Res.50, 383 (1975)

    Google Scholar 

  • Westergaard, E., Brightman, M. W.: Transport of proteins across normal cerebral arterioles. J. comp. Neurol.152, 17–44 (1973)

    Google Scholar 

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Part of this investigation was carried out in Laboratory of Neuropathology and Neuroanatomical Sciences, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland, U.S.A.

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Westergaard, E. Enhanced vesicular transport of exogenous peroxidase across cerebral vessels, induced by serotonin. Acta Neuropathol 32, 27–42 (1975). https://doi.org/10.1007/BF00686065

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  • DOI: https://doi.org/10.1007/BF00686065

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