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Presynaptic receptor systems on the noradrenergic neurones of rat brain

Naunyn-Schmiedeberg's Archives of Pharmacology volume 299, pages 123–141 (1977)Cite this article

Summary

Occurrence and properties of receptors modulating release of noradrenaline were studied in slices of rat occipital cortex and, less extensively, of rat hypothalamus and cerebellar cortex. The slices were preincubated with 3H-noradrenaline and then superfused and stimulated either electrically at 1–3 Hz or by 15–20 mM potassium.

  1. (1)

    Omission of calcium abolished the electrically and potassium-evoked overflow of tritium. Tetrodotoxin blocked the electrically evoked overflow and reduced the response to potassium. The electrically evoked overflow of total tritium consisted of 80% 3H-noradrenaline and 19% 3H-3,4-dihydroxyphenylglycol (DOPEG). Cocaine strongly decreased the electrically evoked overflow of 3H-DOPEG. The overflow of tritium evoked by 15 mM potassium also contained mainly 3H-noradrenaline with only a minor part of 3H-DOPEG.

  2. (2)

    Both the electrically and the potassium-evoked overflow of tritium were reduced by unlabelled noradrenaline (in the presence of cocaine) and tramazoline, and increased by phentolamine and yohimbine. The changes in the evoked overflow of total tritium reflected approximately proportionate changes of 3H-noradrenaline and 3H-DOPEG.

  3. (3)

    Both the electrically and the potassium-evoked overflow of tritium were reduced by morphine and methionine-enkephalin. 3H-noradrenaline and 3H-DOPEG were proportionately decreased. Dextrorphan, in contrast to its analgesically active enantiomer levorphanol, had no effect. Inhibition by morphine persisted after pretreatment with indometacin.

  4. (4)

    Prostaglandin E1 reduced both the electrically and the potassium-evoked overflow of tritium. 3H-noradrenaline and 3H-DOPEG were proportionately decreased.

  5. (5)

    Phentolamine antagonized the inhibitory effect of noradrenaline, but not that of morphine, enkephalin, and prostaglandin E1. Naloxone antagonized the effect of enkephalin, but not that of tramazoline and prostaglandin E1.

  6. (6)

    Acetylcholine (up to 10−5 M) and oxotremorine (up to 10−4 M) failed to reduce the electrically and potassium-evoked overflow. Moreover, atropine (up to 3×10−6 M) had no effect. Up to 10−3 M acetylcholine (in the presence of atropine) as well as up to 10−4 M nicotine did not change the basal outflow of tritium in the absence of releasing stimuli. 10−3 M nicotine caused an increase which was not changed by hexamethonium or omission of calcium. In contrast to the overflow evoked by electrical stimulation or high potassium, the overflow evoked by nicotine mainly consisted of 3H-DOPEG with only a minor part attributable to 3H-noradrenaline.

  7. (7)

    γ-Aminobutyric acid slightly enhanced both the basal and (maximally by 27%) the electrically evoked overflow. Histamine (in the presence of cocaine) slightly decreased the electrically evoked overflow (maximally by 17%).

  8. (8)

    The following drugs did not change the electrically evoked overflow of tritium: dopamine (in the presence of cocaine), isoprenaline (up to 10−6 M), propranolol (up to 10−6 M), serotonin (in the presence of cocaine), angiotensin I, angiotensin II, saralasin, and substance P.

  9. (9)

    It is concluded that transmitter release from the noradrenergic neurones of several brain areas is modulated by drugs acting on α-adrenoceptors, opiate receptors, and prostaglandin receptors. It seems likely, though by no means certain, that the receptors involved are located on the noradrenergic nerve endings themselves, i.e., that they are presynaptic receptors. No evidence was obtained for presynaptic dopamine, β-, muscarine, nicotine, and angiotensin receptors. This pattern differs from that found in other tissues, thus substantiating marked tissue differences in presynaptic receptor systems.

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Affiliations

  1. Abteilung für Anaesthesiologie, Universität Essen, Hufelandstraße 55, D-4300, Essen, Federal Republic of Germany

    H. D. Taube

  2. Pharmakologisches Institut, Universität Freiburg, Katharinenstraße 29, D-7800, Freiburg, Federal Republic of Germany

    K. Starke

  3. Pharmakologisches Institut, Universität Essen, Hufelandstraße 55, D-4300, Essen, Federal Republic of Germany

    E. Borowski

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  1. H. D. Taube
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Taube, H.D., Starke, K. & Borowski, E. Presynaptic receptor systems on the noradrenergic neurones of rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 299, 123–141 (1977). https://doi.org/10.1007/BF00498554

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Key words

  • Rat brain
  • Noradrenaline release
  • Noradrenaline metabolism
  • Presynaptic receptors
  • Opiate receptors
  • α-adrenoceptors