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. 1983 Apr;78(4):645–653. doi: 10.1111/j.1476-5381.1983.tb09415.x

Release of 3H-amezinium from cortical noradrenergic axons: a model for the study of the α-autoreceptor hypothesis

Liselotte Hedler, Klaus Starke, Anton Steppeler
PMCID: PMC2044756  PMID: 6303483

Abstract

1 [3H]-amezinium is taken up selectively into noradrenergic axons and their transmitter-storing vesicles and is released from these axons by action potentials. We used it as a non-α-adrenergic marker in order to study the α-adrenergic autoinhibition of noradrenaline release.

2 Rat occipitocortical slices were preincubated with [3H]-amezinium 0.03 μM and then superfused and stimulated electrically (3 Hz for 3 min). The stimulation-evoked overflow of tritium was measured in six groups of slices: from saline-pretreated rats; from saline-pretreated rats, the slices being exposed to exogenous noradrenaline before preincubation with [3H]-amezinium; from saline-treated rats, slices from which were exposed simultaneously to noradrenaline and cocaine before preincubation with [3H]-amezinium; from rats in which noradrenaline stores had been depleted by pretreatment with α-methyltyrosine (α-MT); from α-MT-treated rats, the slices being exposed to noradrenaline before preincubation with [3H]-amezinium; and from α-MT-treated rats, slices from which were exposed to noradrenaline plus cocaine before preincubation with [3H]-amezinium.

3 The stimulation-evoked overflow of tritium, expressed as a percentage of the tritium content of the tissue, was 1.15% in slices from saline-pretreated rats, and was similar in slices from saline-pretreated rats after exposure to noradrenaline or noradrenaline plus cocaine. It was 2.56% in slices from α-MT-treated rats, 1.20% from α-MT-treated rats after exposure to noradrenaline, and 2.88% from α-MT-treated rats after exposure to noradrenaline plus cocaine.

4 Yohimbine 0.1 and 1 μM increased the stimulation-evoked overflow of tritium in slices from all groups of saline-pretreated rats and in those slices from α-MT rats that had been in contact with exogenous noradrenaline. Yohimbine did not change the evoked overflow in slices from α-MT rats that had not been exposed to noradrenaline, or had been exposed to noradrenaline plus cocaine.

5 Clonidine 0.01-1 μM decreased the stimulation-evoked overflow of tritium moderately in slices from saline-pretreated rats, markedly in slices from α-MT-treated rats, and moderately again when the latter slices had been exposed to noradrenaline.

6 It is concluded that the action potential-evoked release of [3H]-amezinium as well as the modulation of this release by yohimbine and clonidine depend on the presence or absence of α-adrenergic autoinhibition caused by the co-secretion of noradrenaline. When there is co-secretion of noradrenaline, the evoked release of [3H]-amezinium is relatively small, yohimbine increases the release, and clonidine can cause only moderate inhibition. When there is no or very little co-secretion of noradrenaline, the evoked release of [3H]-amezinium is at least doubled, yohimbine causes no further increase and clonidine produces strong inhibition.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auch-Schwelk W., Starke K., Steppeler A. Experimental conditions required for the enhancement by alpha-adrenoceptor antagonists of noradrenaline release in the rabbit ear artery. Br J Pharmacol. 1983 Mar;78(3):543–551. doi: 10.1111/j.1476-5381.1983.tb08814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bacq Z. M. Les contröles de la libération des médiateurs aux terminaisons des nerf adrénergiques. J Physiol (Paris) 1976;72(4):371–473. [PubMed] [Google Scholar]
  3. Borowski E., Starke K., Ehrl H., Endo T. A comparison of pre- and postsynaptic effects of alpha-adrenolytic drugs in the pulmonary artery of the rabbit. Neuroscience. 1977;2(2):285–296. doi: 10.1016/0306-4522(77)90095-1. [DOI] [PubMed] [Google Scholar]
  4. Cubeddu L., Weiner N. Nerve stimulation-meditated overflow of norepinephrine and dopamine-beta-hydroxylase. III. Effects of norepinephrine depletion on the alpha presynaptic regulation of release. J Pharmacol Exp Ther. 1975 Jan;192(1):1–14. [PubMed] [Google Scholar]
  5. Dixon W. R., Mosimann W. F., Weiner N. The role of presynatpic feedback mechanisms in regulation of norepinephrine release by nerve stimulation. J Pharmacol Exp Ther. 1979 May;209(2):196–204. [PubMed] [Google Scholar]
  6. Enero M. A., Langer S. Z. Influence of reserpine-induced depletion of noradrenaline on the negative feed-back mechanism for transmitter release during nerve stimulation. Br J Pharmacol. 1973 Oct;49(2):214–225. doi: 10.1111/j.1476-5381.1973.tb08367.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Farnebo L. O., Hamberger B., Jonsson G. Release of ( 3 H)noradrenaline and ( 3 H)dopamine from field stimulated cerebral cortex slices. Effect of tyrosine hydroxylase and dopamine- -hydroxylase inhibition. J Neurochem. 1971 Dec;18(12):2491–2500. doi: 10.1111/j.1471-4159.1971.tb00205.x. [DOI] [PubMed] [Google Scholar]
  8. Göthert M., Huth H., Schlicker E. Characterization of the receptor subtype involved in alpha-adrenoceptor-mediated modulation of serotonin release from rat brain cortex slices. Naunyn Schmiedebergs Arch Pharmacol. 1981 Nov;317(3):199–203. doi: 10.1007/BF00503816. [DOI] [PubMed] [Google Scholar]
  9. Hedler L., Stamm G., Weitzell R., Starke K. Functional characterization of central alpha-adrenoceptors by yohimbine diastereomers. Eur J Pharmacol. 1981 Mar 5;70(1):43–52. doi: 10.1016/0014-2999(81)90430-1. [DOI] [PubMed] [Google Scholar]
  10. Kalsner S. The role of calcium in the effects of noradrenaline and phenoxybenzamine on adrenergic transmitter release from atria: no support for negative feedback of release. Br J Pharmacol. 1981 Jun;73(2):363–371. doi: 10.1111/j.1476-5381.1981.tb10430.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Langer S. Z. Presynaptic regulation of the release of catecholamines. Pharmacol Rev. 1980 Dec;32(4):337–362. [PubMed] [Google Scholar]
  12. Lenke D., Gries J., Kretzschmar R. Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action. Arzneimittelforschung. 1981;31(9A):1558–1565. [PubMed] [Google Scholar]
  13. Reichenbacher D., Reimann W., Starke K. alpha-Adrenoceptor-mediated inhibition of noradrenaline release in rabbit brain cortex slices. Receptor properties and role of the biophase concentration of noradrenaline. Naunyn Schmiedebergs Arch Pharmacol. 1982 Apr;319(1):71–77. doi: 10.1007/BF00491481. [DOI] [PubMed] [Google Scholar]
  14. Reimann W., Steinhauer H. B., Hedler L., Starke K., Hertting G. Effect of prostaglandins D2, E2 and F2alpha on catecholamine release from slices of rat and rabbit brain. Eur J Pharmacol. 1981 Feb 19;69(4):421–427. doi: 10.1016/0014-2999(81)90445-3. [DOI] [PubMed] [Google Scholar]
  15. Starke K. Alpha sympathomimetic inhibition of adrenergic and cholinergic transmission in the rabbit heart. Naunyn Schmiedebergs Arch Pharmacol. 1972;274(1):18–45. doi: 10.1007/BF00501004. [DOI] [PubMed] [Google Scholar]
  16. Starke K., Altmann K. P. Inhibition of adrenergic neurotransmission by clonidine: an action on prejunctional -receptors. Neuropharmacology. 1973 Apr;12(4):339–347. doi: 10.1016/0028-3908(73)90093-2. [DOI] [PubMed] [Google Scholar]
  17. Starke K., Montel H., Gayk W., Merker R. Comparison of the effects of clonidine on pre- and postsynaptic adrenoceptors in the rabbit pulmonary artery. Alpha-sympathomimetic inhibition of Neurogenic vasoconstriction. Naunyn Schmiedebergs Arch Pharmacol. 1974;285(2):133–150. doi: 10.1007/BF00501149. [DOI] [PubMed] [Google Scholar]
  18. Starke K. Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol. 1977;77:1–124. doi: 10.1007/BFb0050157. [DOI] [PubMed] [Google Scholar]
  19. Starke K., Wagner J., Schümann H. J. Adrenergic neuron blockade by clonidine: comparison with guanethidine and local anesthetics. Arch Int Pharmacodyn Ther. 1972 Feb;195(2):291–308. [PubMed] [Google Scholar]
  20. Steppeler A., Döring C., Hedler L., Starke K. Effect of amezinium on the release and catabolism of 3H-monoamines in brain slices. Biochem Pharmacol. 1982 Jul 15;31(14):2395–2402. doi: 10.1016/0006-2952(82)90535-4. [DOI] [PubMed] [Google Scholar]
  21. Steppeler A., Pfändler R., Hedler L., Starke K. An analysis of the effects of amezinium on postganglionic sympathetic neurones. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):1–11. doi: 10.1007/BF00498425. [DOI] [PubMed] [Google Scholar]
  22. Steppeler A., Starke K. Fate of [3H]amezinium in sympathetically innervated rabbit tissues. Biochem Pharmacol. 1982 Mar 15;31(6):1075–1080. doi: 10.1016/0006-2952(82)90345-8. [DOI] [PubMed] [Google Scholar]
  23. Steppeler A., Starke K. Selective inhibition by amezinium of intraneuronal monoamine oxidase. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):13–16. doi: 10.1007/BF00498426. [DOI] [PubMed] [Google Scholar]
  24. Traut M., Brode E., Hoffmann H. D. Pharmacology of amezinium, a novel antihypotensive drug. IV. Biochemical investigations of the mechanism of action. Arzneimittelforschung. 1981;31(9A):1566–1574. [PubMed] [Google Scholar]
  25. Vizi E. S. Presynaptic modulation of neurochemical transmission. Prog Neurobiol. 1979;12(3-4):181–290. doi: 10.1016/0301-0082(79)90011-x. [DOI] [PubMed] [Google Scholar]
  26. Vizi E. S., Somogyi G. T., Hadházy P., Knoll J. Effect of duration and frequency of stimulation on the presynaptic inhibition by alpha-adrenoceptor stimulation of the adrenergic transmission. Naunyn Schmiedebergs Arch Pharmacol. 1973;280(1):79–91. doi: 10.1007/BF00505357. [DOI] [PubMed] [Google Scholar]
  27. Wemer J., Frankhuyzen A. L., Mulder A. H. Pharmacological characterization of presynaptic alpha-adrenoceptors in the nucleus tractus solitarii and the cerebral cortex of the rat. Neuropharmacology. 1982 Jun;21(6):499–506. doi: 10.1016/0028-3908(82)90039-9. [DOI] [PubMed] [Google Scholar]
  28. Westfall T. C. Local regulation of adrenergic neurotransmission. Physiol Rev. 1977 Oct;57(4):659–728. doi: 10.1152/physrev.1977.57.4.659. [DOI] [PubMed] [Google Scholar]

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