Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1973 Dec;49(4):614–627. doi: 10.1111/j.1476-5381.1973.tb08537.x

Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria

D M Paton
PMCID: PMC1776596  PMID: 4788035

Abstract

1. The mechanism of efflux of (-)-[3H]-noradrenaline was examined in rabbit atria, which were pretreated with reserpine and pargyline.

2. Between 40 and 100 min, efflux occurred predominantly from a single intraneuronal compartment.

3. Efflux was rapidy increased by (-)- and (+)-noradrenaline, tyramine and (±)-metaraminol, but not by (±)-isopropylnoradrenaline or (±)-normetanephrine. The increase in efflux produced by (-)-noradrenaline was inhibited by cocaine and desipramine but not by lidocaine.

4. Spontaneous effluxes, and those accelerated by (-)-noradrenaline, were temperature-sensitive.

5. Efflux was increased by ouabain, omission of K+, metabolic inhibition and lowering of the external Na+ concentration. These effects were significantly reduced by cocaine and desipramine but not by lidocaine.

6. These findings provide evidence that the efflux of [3H]-noradrenaline from adrenergic nerves occurs by a cocaine-sensitive, carrier-mediated process. The characteristics of the efflux process are compatible with, but not conclusive proof for, the Na+-gradient hypothesis.

Full text

PDF
614

Selected References

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

  1. Bogdanski D. F., Brodie B. B. The effects of inorganic ions on the storage and uptake of H3-norepinephrine by rat heart slices. J Pharmacol Exp Ther. 1969 Feb;165(2):181–189. [PubMed] [Google Scholar]
  2. Foster R. W., O'Donnell S. R. Some evidence of the active uptake of noradrenaline in the guinea-pig isolated trachea. Br J Pharmacol. 1972 May;45(1):71–82. doi: 10.1111/j.1476-5381.1972.tb09578.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gillis C. N., Paton D. M. Cation dependence of sympathetic transmitter retention by slices of rat ventricle. Br J Pharmacol Chemother. 1967 Mar;29(3):309–318. doi: 10.1111/j.1476-5381.1967.tb01962.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. HAMBERGER B., MALMFORS T., NORBERG K. A., SACHS C. UPTAKE AND ACCUMULATION OF CATECHOLAMINES IN PERIPHERAL ADRENERGIC NEURONS OF RESERPINIZED ANIMALS, STUDIED WITH A HISTOCHEMICAL METHOD. Biochem Pharmacol. 1964 Jun;13:841–844. doi: 10.1016/0006-2952(64)90026-7. [DOI] [PubMed] [Google Scholar]
  5. Iversen L. L., Glowinski J., Axelrod J. The uptake and storage of H3-norepinephrine in the reserpine-pretreated rat heart. J Pharmacol Exp Ther. 1965 Nov;150(2):173–183. [PubMed] [Google Scholar]
  6. Iversen L. L., Jarrott B., Simmonds M. A. Differences in the uptake, storage and metabolism of (+)- and (-)-noradrenaline. Br J Pharmacol. 1971 Dec;43(4):845–855. doi: 10.1111/j.1476-5381.1971.tb07221.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Iversen L. L. Role of transmitter uptake mechanisms in synaptic neurotransmission. Br J Pharmacol. 1971 Apr;41(4):571–591. doi: 10.1111/j.1476-5381.1971.tb07066.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jarrott B. Uptake and metabolism of catecholamines in the perfused hearts of different species. Br J Pharmacol. 1970 Apr;38(4):810–821. doi: 10.1111/j.1476-5381.1970.tb09890.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lindmar R., Löffelholz K. Differential effects of hypothemia on neuronal efflux, release and uptake of noradrenaline. Naunyn Schmiedebergs Arch Pharmacol. 1972;274(4):410–414. doi: 10.1007/BF00501278. [DOI] [PubMed] [Google Scholar]
  10. Munson J. L., Paton D. M. Coupled Na + -K + pumping in rabbit detrusor muscle. Comp Biochem Physiol B. 1972 Sep 15;43(1):97–108. doi: 10.1016/0305-0491(72)90205-2. [DOI] [PubMed] [Google Scholar]
  11. Osman F. H., Munson J. L., Paton D. M. Factors affecting extracellular space measurements in rabbit detrusor muscle. Comp Biochem Physiol A Comp Physiol. 1973 Aug 1;45(4):1047–1055. doi: 10.1016/0300-9629(73)90341-1. [DOI] [PubMed] [Google Scholar]
  12. Paton D. M. Effect of local anaesthetics on the accumulation of ( 3 H)-metaraminol by rabbit atria and vasa deferentia. Experientia. 1972 Oct 15;28(10):1191–1192. doi: 10.1007/BF01946163. [DOI] [PubMed] [Google Scholar]
  13. Paton D. M. Effects of Na+ and K+ on the uptake of metaraminol by rabbit ventricular slices. Br J Pharmacol. 1971 Jan;41(1):65–75. doi: 10.1111/j.1476-5381.1971.tb09936.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Paton D. M. Evidence for carrier-mediated efflux of noradrenaline from the axoplasm of adrenergic nerves in rabbit atria. J Pharm Pharmacol. 1973 Mar;25(3):265–267. doi: 10.1111/j.2042-7158.1973.tb10639.x. [DOI] [PubMed] [Google Scholar]
  15. Paton D. M. Metabolic requirements for the uptake of noradrenaline by isolated atria and vas deferens of the rabbit. Pharmacology. 1972;7(2):78–88. doi: 10.1159/000136275. [DOI] [PubMed] [Google Scholar]
  16. Rangachari P. K., Paton D. M., Daniel E. E. Aerobic and glycolytic support of sodium pumping and contraction in rat myometrium. Am J Physiol. 1972 Nov;223(5):1009–1015. doi: 10.1152/ajplegacy.1972.223.5.1009. [DOI] [PubMed] [Google Scholar]
  17. Schultz S. G., Curran P. F. Coupled transport of sodium and organic solutes. Physiol Rev. 1970 Oct;50(4):637–718. doi: 10.1152/physrev.1970.50.4.637. [DOI] [PubMed] [Google Scholar]
  18. Starke K. Influence of extracellular noradrenaline on the stimulation-evoked secretion of noradrenaline from sympathetic nerves: evidence for an -receptor-mediated feed-back inhibition of noradrenaline release. Naunyn Schmiedebergs Arch Pharmacol. 1972;275(1):11–23. doi: 10.1007/BF00505064. [DOI] [PubMed] [Google Scholar]
  19. Sugrue M. F., Shore P. A. The mode of sodium dependency of the adrenergic neuron amide carrier. Evidence for a second, sodium-dependent, optically specific and reserpine-sensitive system. J Pharmacol Exp Ther. 1969 Dec;170(2):239–245. [PubMed] [Google Scholar]
  20. White T. D., Keen P. The role of internal and external Na+ and K+ on the uptake of [3H] noradrenaline by synaptosomes prepared from rat brain. Biochim Biophys Acta. 1970;196(2):285–295. doi: 10.1016/0005-2736(70)90016-7. [DOI] [PubMed] [Google Scholar]
  21. White T. D., Paton D. M. Effects of external Na + and K + on the initial rates of noradrenaline uptake by synaptosomes prepared from rat brain. Biochim Biophys Acta. 1972 Apr 14;266(1):116–127. doi: 10.1016/0005-2736(72)90126-5. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES