Skip to main content
Log in

Quinacrine affinity of endocrine cell systems containing dense core vesicles as visualized by fluorescence microscopy

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Summary

Intravenous injections of low amounts of the fluorescent antimalarial acridine derivative quinacrine into rats and mice lead to selective high affinity binding of the drug, which can be visualized by fluorescence microscopy, to several hormone-producing cell systems. Injection of 1 mg/kg causes strong drug accumulation in the granules of renin-producing juxtaglomerular cells of the kidney and in several types of cells of the pancreatic islets, and a moderate binding to parafollicular cells in the thyroid gland, chromaffin cells of the adrenal medulla, several gastrointestinal cell systems including APUD cells, cells of the anterior pituitary gland, neurosecretory neurons and mast cells. These different cell systems all have large dense-core storage granules.

The present results, together with our earlier finding of a population of gastrointestinal nerve fibers which demonstrate a similar selective high affinity binding of quinacrine might all be explained by a binding of quinacrine to large dense-core storage granules, since such granules are known to be present also in certain gastrointestinal nerve fibers. This is further supported by the finding that endocrine cell systems lacking such granules, such as steroid producing cells in the adrenal cortex and testis, do not accumulate quinacrine. Peptide storage, possibly mediated by or accompanied by purines such as ATP within the granules or an acidic intragranular pH constitute possible binding mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albert, A.: The acridines. Their preparation, physical, chemical and biological properties and uses. London: Edward Arnold Ltd. (1966)

    Google Scholar 

  • Ålund, M.: Semiquantitative estimations of quinacrine fluorescence in intestinal nerve fibres. Histochemistry 58, 153–161 (1978)

    Google Scholar 

  • Ålund, M., Olson, L.: Characterization of quinacrine-binding gastro-intestinal nerve fibres: A fluorescence histochemical method for non-adrenergic, non-cholinergic nerves. In: Abstracts of 2nd European Neurosci. Meet. Florence Sept. 4–9, 1978. Neurosci. Lett. Suppl. 1, 265 (1978)

  • Ålund, M., Olson, L.: Depolarization-induced decreases in fluorescence intensity of gastro-intestinal quinacrine-binding nerves. Brain Res. 166, 121–137 (1979)

    Google Scholar 

  • Bargmann, W., Lindner, E., Andres, K.H.: Über Synapsen an endokrinen Epithelzellen und die Definition sekretorischer Neurone. Z. Zellforsch. 77, 282–298 (1967)

    Google Scholar 

  • Baumgarten, H.G., Holstein, A.L., Owman, Ch.: Auerbach's plexus of mammals and man: electron microscopic identification of three different types of neuronal processes in myenteric ganglia of the large intestine from rhesus monkeys, guinea-pigs and man. Z. Zellforsch. 106, 376–397 (1970)

    Google Scholar 

  • Blaschko, H., Born, G.V.R., D'Iorio, A., Eade, N.R.: Observation on the distribution of catecholamines and adenosinetriphosphate in the bovine adrenal medulla. J. Physiol. (Lond.) 133, 548–557 (1956)

    Google Scholar 

  • Blaschko, H., Hagen, J.M., Hagen, P.: Mitochondrial enzymes and chromaffine granules. J. Physiol. (Lond.) 139, 316–322 (1957)

    Google Scholar 

  • Burnstock, G.: Neural nomenclature. Nature 299, 282–283 (1971)

    Google Scholar 

  • Burnstock, G.: Purinergic nerves. Pharmacol. Rev. 24, 509–581 (1972)

    Google Scholar 

  • Burnstock, G.: Purinergic transmission. In: Handbook of Psychopharmacology Vol. 5 (L.L. Iversen, S.D. Iversen, S.H. Snyder, eds.) pp. 131–194. New York: Plenum Publishing Corporation (1975)

    Google Scholar 

  • Burnstock, G.: Do some nerve cells release more than one transmitter? Neuroscience 1, 239–248 (1976)

    Google Scholar 

  • Burnstock, G., Campbell, G., Satchell, D.G., Smythe, A.: Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. Brit. J. Pharmacol. 40, 668–688 (1970)

    Google Scholar 

  • Burnstock, G., Cocks, T., Crowe, R.: Evidence for purinergic innervation of the anococcygeus muscle. Brit. J. Pharmacol. 64, 13–20 (1978a)

    Google Scholar 

  • Burnstock, G., Cocks, T., Crowe, R., Kasakov, L.: Purinergic innervation of the guinea-pig urinary bladder. Brit. J. Pharmacol. 63, 125–138 (1978b)

    Google Scholar 

  • Burnstock, G., Crowe, R., Wong, H.: Comparative pharmacological and histochemical evidence for purinergic inhibitory innervation of the portal vein of the rabbit but not guinea-pig. Brit. J. Pharmacol. 65, 377–388 (1979)

    Google Scholar 

  • Canese, M.G., Bussolati, G.: Immuno-electron-cytochemical localization of the somatostatin cells in the human antral mucosa. J. Histochem. Cytochem. 25, 1111–1118 (1977)

    Google Scholar 

  • Capen, C.C., Rowland, G.N.: The ultrastructure of the parathyroid glands of young cats. Anat. Rec. 162, 327–340 (1968)

    Google Scholar 

  • Caspersson, T., Lindsten, J., Lomakka, G., Möller, A., Zech, L.: The use of fluorescence techniques for the recognition of mammalian chromosomes and chromosome regions. Int. Rev. Exp. Path. 11, 1–72 (1972)

    Google Scholar 

  • Chubb, I.W.: The release of non-transmitter substances. In: Synapses (G.A. Cottrell, P.N.R. Usherwood, eds.) pp. 264–290. New York: Academic Press (1977)

    Google Scholar 

  • Comings, E.E., Kovacs, B.W., Avelino, E., Harris, D.C.: Mechanism of chromosome banding V. Quinacrine banding. Chromosoma (Berl.) 50, 111–145 (1975)

    Google Scholar 

  • Corrodi, H., Jonsson, G.: The formaldehyde fluorescence method for the histochemical demonstration of biogenic monoamines. A review of the methodology. J. Histochem. Cytochem. 15, 65–78 (1967)

    Google Scholar 

  • Coupland, R.E.: Electron microscopic observations on the structure of the rat adrenal medulla. I. The ultrastructure and organization of chromaffin cells in the normal adrenal medulla. J. Anat. 99, 231–254 (1965)

    Google Scholar 

  • Crowe, R., Whitear, M.: Quinacrine fluorescence of Merkel cells in Xenopus laevis. Cell Tissue Res. 190, 273–283 (1978)

    Google Scholar 

  • David-Ferreira, J.F.: The blood platelet: Electron microscopic studies. Int. Rev. Cytol. 17, 99–148 (1964)

    Google Scholar 

  • Dencker, L., Lindquist, N.G., Tjälve, H.: Uptake of 14C-labelled chloroquine and an 125I-labelled chloroquine analogue in some polypeptide hormone producing cell systems. Med. Biol. 54, 62–68 (1976)

    Google Scholar 

  • Edelman, R., Hartroft, P.M.: Localization of renin in juxtaglomerular cells of rabbit and dog through use of the fluorescent-antibody technique. Circ. Res. 9, 1069–1077 (1961)

    Google Scholar 

  • Elfvin, L.-G.: The fine structure of the cell surface of chromaffin cells in the rat adrenal medulla. J. Ultrastruct. Res. 12, 263–286 (1965)

    Google Scholar 

  • Falck, B., Hillarp, N.-Å., Högberg, B.: Content and intracellular distribution of adenosine triphosphate in cow adrenal medulla. Acta Physiol. Scand. 36, 360–376 (1956)

    Google Scholar 

  • Falck, B., Hillarp, N.-Å., Thieme, G., Torp, A.: Fluorescence of catecholamines and related compounds condensed with formaldehyde. J. Histochem. Cytochem. 10, 348–354 (1962)

    Google Scholar 

  • Fujita, T.: The gastro-intestinal endocrine cell and its paraneuronic nature. In: Chromaffin, Enterochromaffin and Related Cells (R.E. Coupland, T. Fujita, eds.) pp. 191–208. Amsterdam, New York: Elsevier (1976)

    Google Scholar 

  • Goldsmith, P.C., Ganong, W.F.: Ultrastructural localization of luteinizing hormone-releasing hormone in the median eminence of the rat. Brain Res. 97, 181–193 (1975)

    Google Scholar 

  • Goldsmith, P.C., Rose, J.C., Arimura, A., Ganong, W.F.: Ultrastructural localization of somatostatin in pancreatic islets of the rat. Endocrinology 97, 1061–1064 (1975)

    Google Scholar 

  • Hartroft, P.M., Newmark, L.: Electron microscopy of renal juxtaglomerular cells. Anat. Rec. 139, 185–199 (1961)

    Google Scholar 

  • Hillarp, N.-Å., Högberg, B., Nilsson, B.: Adenosine triphosphate in the adrenal medulla of the cow. Nature (Lond.) 176, 1032–1033 (1955)

    Google Scholar 

  • Hökfelt, T., Elde, R., Fuxe, K., Johansson, O., Ljungdahl, Å., Goldstein, M., Luft, R., Efendic, S., Nilsson, G., Terenius, L., Ganten, D., Jeffcoate, S.L., Rehfeld, J., Said, S., Perez de la Mora, M., Possani, L., Tapia, R., Teran, L., Palacios, R.: Aminergic and Peptidergic Pathways in the Nervous System with Special Reference to the Hypothalamus. In: The hypothalamus (S. Reichlin, R.J. Baldessarini, J.B. Martin, eds.) pp. 69–135. New York: Raven Press (1978a)

    Google Scholar 

  • Hökfelt, T., Elde, R., Johansson, O., Ljungdahl, Å., Schultzberg, M., Fuxe, K., Goldstein, M., Nilsson, G., Pernow, B., Terenius, L., Ganten, D., Jeffcoate, S.L., Rehfeld, J., Said, S.: Distribution of Peptide-Containing Neurones. In: Psychopharmacology: a generation of progress (M.A. Lipton, A.D.I. Mascio, K.F. Killiam, eds.) pp. 39–65. New York: Raven Press (1978b)

    Google Scholar 

  • Irvin, J.L., Irvin, E.M.: The interaction of quinacrine with adenine nucleotides. J. Biol. Chem. 210, 45–56 (1954)

    Google Scholar 

  • Johnson, R.G., Scarpa, A., Salganicoff, L.: The internal pH of isolated serotonin containing granules of pig platelets. J. Biol. Chem. 253, 7061–7068 (1978)

    Google Scholar 

  • Kurnick, N.B., Radcliffe, I.E.: Reaction between DNA and quinacrine and other antimalarials. J. Lab. Clin. Med. 60, 669–688 (1962)

    Google Scholar 

  • Leclerc, R., Pelletier, G., Puviani, R., Arimura, A., Shally, A.V.: Immuno-histochemical localization of somatostatin in endocrine cells of the rat stomach. Molec. Cell. Endocrinol. 4, 257–261 (1976)

    Google Scholar 

  • Lermann, L.S.: Structural considerations in the interaction of DNA and acridines. J. Molec. Biol. 3, 18–30 (1961)

    Google Scholar 

  • Lermann, L.S.: The structure of the DNA acridine complex. Proc. Natl. Acad. Sci. (Wash.) 49, 94–102 (1963)

    Google Scholar 

  • Nakagima, K., Yamazaki, Y., Isunoda, Y.: An electron microscopic study of the human fetal parathyroid gland. Z. Zellforsch. 85, 89–95 (1968)

    Google Scholar 

  • Olson, L., Ålund, M.: Quinacrine binding nerves: Presence in the mouse anococcygeal muscle and disappearance after transection. Med. Biol. 57, 182–186 (1979)

    Google Scholar 

  • Olson, L., Ungerstedt, U.: A simple high capacity freeze-drier for histochemical use. Histochemie 22, 8–19 (1970)

    Google Scholar 

  • Olson, L., Ålund, M., Norberg, K.-A.: Fluorescence-microscopical demonstration of a population of gastro-intestinal nerve fibres with a selective affinity for quinacrine. Cell Tissue Res. 171, 407–423 (1976)

    Google Scholar 

  • Pearse, A.G.E., Coulling, I., Weavers, B., Friesen, S.: The endocrine polypeptide cells of the human stomach, duodenum and jejunum. Gut 11, 649–658 (1970)

    Google Scholar 

  • Pelletier, G., Labrie, F., Puviani, R., Arimura, A., Schally, A.V.: Electron microscopic immunohistochemical localization of luteinizing hormone-releasing hormone in the rat median eminence. Endocrinology 95, 314–317 (1974a)

    Google Scholar 

  • Pelletier, G., Labrie, F., Arimura, A., Schally, A.V.: Electron microscopic immunohistochemical localization of growth hormone release inhibiting hormone (somatostatin) in the rat median eminence. Am. J. Anat. 140, 445–450 (1974b)

    Google Scholar 

  • Picotti, G.B., da Prada, M., Pletscher, A.: Uptake and liberation of Mepacrine in blood platelets. Arch. Pharmacol. 292, 127–131 (1976)

    Google Scholar 

  • Prada, M. da, Pletscher, A.: Accumulation of basic drugs in 5-hydroxytryptamine storage organelles of rabbit blood platelets. Europ. J. Pharmacol. 32, 179–185 (1975)

    Google Scholar 

  • Prada, M. da, Berneis, K.H., Pletschner, A.: Storage of catecholamines in adrenal medullary granules: formation of aggregates with nucleotides. Life Sciences 10, 639–646 (1971)

    Google Scholar 

  • Solcia, E., Capella, C., Vassallo, G., Buffa, R.: Endocrine cells of the gastric mucosa. Int. Rev. Cytol. 42, 223–286 (1975)

    Google Scholar 

  • Solcia, E., Capella, C., Buffa, R., Frigerio, B.: Histochemical and ultrastructural studies on the argentaffin and argyrophil cells of the gut. In: Chromaffin, Enterochromaffin and Related Cells (R.E. Coupland, T. Fujita, eds.) pp. 223–225, Amsterdam, New York: Elsevier (1976)

    Google Scholar 

  • Solcia, E., Polak, J.M., Pearse, A.G.E., Forssmann, W.G., Larsson, L.-I., Sundler, F., Lechago, J., Grimelius, L., Fujita, T., Creutzfeldt, W., Gepts, W., Falkmer, S., Lefranc, G., Heitz, Ph., Hage, E., Buchan, A.M.J., Bloom, S.R., Grossman, M.I.: Lausanne 1977 classification of gastroenteropancreatic endocrine cells. In: Gut Hormones (S.R. Bloom, ed.) pp. 40–48, Thetford, England: Lowe and Brydone (1977)

    Google Scholar 

  • Su, C., Bevan, J., Burnstock, G.: Adenosine triphosphate. Release during stimulation of enteric nerves. Science 173, 337–339 (1971)

    Google Scholar 

  • Tranzer, J.P., da Prada, M., Pletscher, A.: Storage of 5-hydroxytryptamine in megakaryocytes. J. Cell Biol. 52, 191–197 (1972)

    Google Scholar 

  • Weiner, N.: The catecholamines: Biosynthesis storage and release, metabolism and metabolic effects. In: The Hormones, Vol. 4, pp. 403–479. New York: Acad. Press (1964)

    Google Scholar 

  • Yamada, E.: The fine structure of the megakaryocyte in the mouse spleen. Acta Anat. 29, 267–290 (1957)

    Google Scholar 

  • Zelander, T.: The adrenal gland. In: Electron microscopic Anatomy (S.M. Kurtz, ed.) pp. 199–220. New York: Acad. Press (1964)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ålund, M., Olson, L. Quinacrine affinity of endocrine cell systems containing dense core vesicles as visualized by fluorescence microscopy. Cell Tissue Res. 204, 171–186 (1979). https://doi.org/10.1007/BF00234631

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00234631

Key words

Navigation