Summary
The influence of chronic postganglionic sympathetic denervation upon uptake and effects of administereddl-[H]3-Noradrenaline ([H]3-NA) has been investigated using the isolated perfused spleen preparation. The total radioactivity and [H]3-NA was determined in the tissues and in the perfusate. The maximal splenic contraction was measured as change in volume. 108, 216, and 432 nanogramsdl-7-[H]3-NA were infused into the innervated tissues, 54, 108, and 216 nanograms into the denervated. The duration of the infusions in each case was 2 min, and the perfusate was collected for 29 min during and after each infusion.
In the innervated preparations, 53.5% of the radioactivity was found in the tissues, 41% in the perfusate and 5.4% in the bath fluid. In denervated preparations, only 5.6% of the infused radioactivity was found in the tissues, whilst 85% was recovered in the perfusate and 8% in the bath fluid. In the innervated tissues 92% of the radioactivity was recovered in [H]3-NA, whereas in the denervated tissues only 50% was present in [H]3-NA.
In the perfusate of innervated tissues 74% of the total radioactivity was present in [H]3-NA, whilst in the perfusate of the denervated tissues 84% of the total radioactivity was recovered in [H]3-NA.
The sensitivity of the denervated spleens was 2,78 times higher towardsdl-[H]3-NA as compared with the innervated organs. In order to reach similar concentrations of [H]3-NA in the perfusates of the first sampling period, in which where the spleen contractions occur, 2,13 times moredl-[H]3-NA had to be infused into the innervated spleens than in the case of the denervated organs. The cause of the difference between innervated and denervated tissues in respect to sensitivity on the one hand, and rise in NA-concentration in the perfusate on the other hand is discussed.
It is concluded that the supersensitivity following chronic postganglionic sympathetic denervation is produced by the decreased ability of the tissues to take up Noradrenaline into the sympathetic nerve terminale and thereby inactivate it.
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Literatur
Axelrod, J.: The fate of adrenaline and noradrenaline. Ciba Foundation Symposion on Adrenergic Mechanism, 1960; Editors:G. W. Wolstenholme andM. O'Connor.
——, andR. Tomchick: Activation and inhibition of adrenaline metabolism. Nature (Lond.)184, 2027 (1959).
——, andR. Tomchick: The physiological disposition of [H]3-epinephrine and its metabolite metanephrine. J. Pharmacol. exp. Ther.127, 251 (1959).
Björling, M., andB. Waldeck: The disappearance ofl-14C-noradrenaline formed from14C-dopamine in vivo. Life Sci.4, 2239 (1965).
Bray, G. A.: A simple efficient liquid scintillator for counting aqueous solutions in a liquid scintillation counter. Analyt. Biochem.1, 279 (1960).
Crout, J. R., C. R. Creveling, andS. Udenfriend: Norepinephrine metabolism in rat brain and heart. J. Pharmacol. exp. Ther.132, 269 (1961).
Euler, U. S. von, andF. Lishajko: Stereospecific catecholamine uptake in rabbit hearts depleted by decaborane. Int. J. Neuropharmacol.4, 273 (1965).
Fleckenstein, A., u.H. Bass: Zum Mechanismus der Wirkungsverstärkung und Wirkungsabschwächung sympathomimetischer Amine durch Cocain und andere Pharmaka. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.220, 143 (1953).
Gillespie, J. S., andS. M. Kirpekar: The inactivation of infused noradrenaline by the cat spleen. J. Physiol. (Lond.)176, 205 (1965a).
-- The localization of endogenous and infused noradrenaline in the spleen. J. Physiol. (Lond.)179, 46 P (1965b).
Haefely, W., A. Hürlimann, andH. Thoenen: A quantitative study of the effect of cocaine on the response of the cat nictitating membrane to nerve stimulation and to injected noradrenaline. Brit. J. Pharmacol.22, 5 (1964).
Hertting, G.: Effect of drugs and sympathetic denervation on noradrenaline uptake and binding in animal tissues. Pharmacol. of Cholinergic and Adrenergic Transmission Proc. Soc. Intern. Pharmacol. Meeting, 1963, vol. 3, p. 277. Pergamon Press 1965.
——, andJ. Axelrod: Fate of tritiated noradrenaline at the sympathetic nerve-endings. Nature (Lond.)192, 172 (1961).
——, andL. G. Whitby: Lack of uptake of catecholamines after chronic denervation of sympathetic nerves. Nature (Lond.)189, 66 (1961a).
—— andL. G. Whitby: Effect of drugs on the uptake and metabolism of [H]3-norepinephrine. J. Pharmacol. exp. Ther.134, 146 (1961).
——, u.T. Schiefthaler: Beziehung zwischen Durchflußgröße und Noradrenalin-freisetzung bei Nervenreizung der isoliert durchströmten Katzenmilz. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.246, 13 (1963).
—— The effect of stellate ganglion excision on the catecholamine content and the uptake of [H]3-norepinephrine in the heart of the cat. Int. J. Neuropharmacol.3, 65 (1964).
——, andJ. Suko: Influence of angiotensin, vasopressin or changes in flow rate on vasoconstriction, changes in volume and [H]3-noradrenaline release following postganglionic sympathetic nerve stimulation in the isolated cat spleen. Brit. J. Pharmacol.26, 686 (1966).
—— u.S. Widhalm: Über den Mechanismus der Potenzierung der Katecholaminwirkung nach chronisch postganglionärer sympathischer Denervierung. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.251, 164 (1965).
Iversen, L. L.: The uptake of noradrenaline by the isolated perfused rat heart. Brit. J. Pharmacol.21, 523 (1963).
—— The uptake of catechol amines at high perfusion concentrations in the rat isolated heart: A novel catechol amine uptake process. Brit. J. Pharmacol.25, 18 (1965a).
—— Inhibition of noradrenaline uptake by drugs. Advanc. Drug. Res.2, 1 (1965b).
——, andJ. Axelrod: The physiologic disposition and metabolism of norepinephrine in immunosympathectomized animals. J. Pharmacol. exp. Ther.151, 273 (1966).
—— Reduced uptake of tritiated noradrenaline in tissues of immunosympathectomized animals. Nature (Lond.)206, 1222 (1965).
Kirpekar, S. M., P. Cervoni, andR. F. Furchgott: Catecholamine content of the cat nictitating membrane following procedures sensitizing it to norepinephrine. J. Pharmacol. exp. Ther.135, 180 (1962).
Kopin, I. J., G. Hertting, andE. K. Gordon: Fate of norepinephrine-[H]3 in the isolated perfused rat heart. J. Pharmacol. exp. Ther.138, 34 (1962).
Langer, S. Z., andU. Trendelenburg: The onset of denervation supersensitivity. J. Pharmacol. exp. Ther.151, 73 (1966).
Levi-Montalcini, R., andP. U. Angeletti: Noradrenaline and monoaminoxidase content in immunosympathectomized animals. Int. J. Neuropharmacol.1, 161 (1962).
Malmfors, T., andCh. Sachs: Direct studies on the disappearance of the transmitter and changes in the uptake-storage mechanisms of degenerating adrenergic nerves. Acta physiol. scand.64, 211 (1965).
Muscholl, E.: Die Hemmung der Noradrenalin-Aufnahme des Gewebes durch Cocain. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.240, 8 (1960a).
—— Die Hemmung der Noradrenalinaufnahme des Herzens durch Reserpin und die Wirkung von Tyramin. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.240, 234 (1960b).
—— Effect of cocain and related drugs on the uptake of noradrenaline by heart and spleen. Brit. J. Pharmacol.16, 352 (1961).
Potter, L. T., T. Cooper, V. L. Willman, andD. E. Wolfe: Synthesis, binding, release and metabolism of norepinephrine in normal and transplanted dog heart. Circulat. Res.16, 468 (1965).
Sjöqvist, F., E. Titus, I. A. Michaelson, P. Taylor jr., andK. C. Richardson: Uptake and metabolism ofdl-norepinephrine-7-[H]3 in tissues of immunosympathectomized mice and rats. Life Sci.4, 1125 (1965).
Smith, C. B., U. Trendelenburg, S. Z. Langer, andT. H. Tsai: The relation of retention of norepinephrine-[H]3 to the norepinephrine content of the nictitating membrane of the spinal cat during development of denervation supersensitivity. J. Pharmacol. exp. Ther.151, 87 (1966).
Suko, J., u.G. Hertting: Abbau von infundiertemdl-7[H]3-Noradrenalin in chronisch denervierten bzw. reserpinvorbehandelten, isoliert durchströmten Katzenmilzen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.253, 87 (1966).
Trendelenburg, U.: The supersentivity caused by cocaine. J. Pharmacol. exp. Ther.125, 55 (1959).
—— Supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol. Rev.15, 225 (1963).
Whitby, L. G., G. Hertting, andJ. Axelrod: Effect of cocain on the disposition of noradrenaline labelled with tritium. Nature (Lond.)187, 604 (1960).
Zaimis, E., L. Berk, andB. A. Callingham: Morphological, biochemical, and functional changes in the sympathetic nervous system of rats treated with nerve growth factor-antiserum. Nature (Lond.)206, 1220 (1965).
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Über einen Teil der Ergebnisse wurde auf der sechsten Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft in Mainz 1965 berichtet (Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.251, 164 (1965).
Diese Untersuchungen wurden mit der Unterstützung des Public Health Service Research Grant No. H-7025 des National Heart Institute, Bethesda, USA, durchgeführt.
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Hertting, G., Suko, J., Widhalm, S. et al. Über den Mechanismus der Potenzierung der Katecholaminwirkung nach chronisch postganglionärer sympathischer Denervierung. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 256, 40–54 (1967). https://doi.org/10.1007/BF00585357
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DOI: https://doi.org/10.1007/BF00585357