Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1983 Jan;78(1):221–231. doi: 10.1111/j.1476-5381.1983.tb09383.x

Stimulation-evoked release of [3H]-noradrenaline by 1, 10 or 100 pulses and its modification through presynaptic alpha 2-adrenoceptors.

I Marshall
PMCID: PMC2044805  PMID: 6297648

Abstract

1 Mice isolated vasa deferentia were loaded with 1-[7,8-3H]-noradrenaline and subsequently field stimulated with 1, 10 or 100 pulses (2 ms pulse width, 1 Hz). The tritium overflow was separated into [3H]-noradrenaline and its 3H-metabolites. 2 The resting release of tritium contained about 7% [3H]-noradrenaline, 33% [3H]-3, 4-dihydroxyphenylglycol ([3H]-DOPEG) and 60% 3H-non-catechols with usually less than 1% [3H]-dihydroxymandelic acid ([3H]-DOMA). The proportion of the tritium as [3H]-noradrenaline increased with stimulation train length to 35% with 100 pulses; this increase in [3H]-noradrenaline was associated with falls in [3H]-DOPEG and 3H-non-catechols. Generally the proportional increase in [3H]-noradrenaline on stimulation was about 10 x total tritium when compared with the resting release. 3 The fractional release of [3H]-noradrenaline per pulse was independent of train length, averaging about 6 x 10(-6). This was reduced by the alpha 2-adrenoceptor agonist clonidine (0.3 - 30 nM) with an IC50 of 4.8 nM (10 pulses at 1 Hz). 4 The alpha 2-adrenoceptor antagonist, yohimbine (10 - 100 nM), did not alter the fractional release of [3H]-noradrenaline elicited by 1 pulse. The antagonist did not change the amount or composition of the resting or evoked tritium overflow. However, yohimbine (1 - 100 nM) increased the fractional release of [3H]-noradrenaline per pulse for trains of 10 or 100 pulses (1 Hz) in a concentration-dependent fashion. An increase above controls was significant only with 100 pulses and yohimbine, 30 nM. 5 The results show that the release of noradrenaline during trains of pulses in the mouse vas deferens can be regulated through presynaptic alpha 2-adrenoceptors. There was no evidence of inhibition by noradrenaline of its own release following a single pulse.

Full text

PDF
221

Selected References

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

  1. ANTON A. H., SAYRE D. F. A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther. 1962 Dec;138:360–375. [PubMed] [Google Scholar]
  2. Dubocovich M. L., Langer S. Z. Influence of the frequency of nerve stimulation on the metabolism of 3H-norepinephrine released from the perfused cat spleen: differences observed during and after the period of stimulation. J Pharmacol Exp Ther. 1976 Jul;198(1):83–101. [PubMed] [Google Scholar]
  3. Dubocovich M. L., Langer S. Z. Negative feed-back regulation of noradrenaline release by nerve stimulation in the perfused cat's spleen: differences in potency of phenoxybenzamine in blocking the pre- and post-synaptic adrenergic receptors. J Physiol. 1974 Mar;237(3):505–519. doi: 10.1113/jphysiol.1974.sp010495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Farnebo L. O., Malamfors T. 3 H-noradrenaline release and mechanical response in the field stimulated mouse vas deferens. Acta Physiol Scand Suppl. 1971;371:1–18. doi: 10.1111/j.1748-1716.1971.tb05210.x. [DOI] [PubMed] [Google Scholar]
  5. Graffe K. H., Stefano F. J., Langer S. Z. Preferential metabolism of (-) 3 H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol. 1973 May 15;22(10):1147–1160. doi: 10.1016/0006-2952(73)90231-1. [DOI] [PubMed] [Google Scholar]
  6. Hughes I. E. The effect of amitriptyline on presynaptic mechanisms in noradrenergic nerves. Br J Pharmacol. 1978 Jun;63(2):315–321. [PMC free article] [PubMed] [Google Scholar]
  7. Hughes J. Differential labelling of intraneuronal noradrenaline stores with different concentrations of (-)-3H-noradrenaline. Br J Pharmacol. 1973 Feb;47(2):428–430. doi: 10.1111/j.1476-5381.1973.tb08342.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hughes J. Evaluation of mechanisms controlling the release and inactivation of the adrenergic transmitter in the rabbit portal vein and vas deferens. Br J Pharmacol. 1972 Mar;44(3):472–491. doi: 10.1111/j.1476-5381.1972.tb07285.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Häggendal J., Malmfors T. The effect of nerve stimulation on the uptake of noradrenaline into the adrenergic nerve terminals. Acta Physiol Scand. 1969 Jan-Feb;75(1):28–32. doi: 10.1111/j.1748-1716.1969.tb04351.x. [DOI] [PubMed] [Google Scholar]
  10. Kalsner S. Limitations of presynaptic adrenoceptor theory: the characteristics of the effects of noradrenaline and phenoxybenzamine on stimulation-induced efflux of [3H]noradrenaline in vas deferens. J Pharmacol Exp Ther. 1980 Feb;212(2):232–239. [PubMed] [Google Scholar]
  11. Kalsner S. Single pulse stimulation of guinea-pig vas deferens and the presynaptic receptor hypothesis. Br J Pharmacol. 1979 Jun;66(2):343–349. doi: 10.1111/j.1476-5381.1979.tb13686.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Marshall I., Nasmyth P. A., Nicholl C. G., Shepperson N. B. alpha-Adrenoceptors in the mouse vas deferens and their effects on its response to electrical stimulation. Br J Pharmacol. 1978 Jan;62(1):147–151. doi: 10.1111/j.1476-5381.1978.tb07018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Marshall I., Nasmyth P. A., Shepperson N. B. Presynaptic alpha-adrenoceptors and [3H]-noradrenaline overflow from the mouse was deferens [proceedings]. Br J Pharmacol. 1978 Mar;62(3):382P–383P. [PMC free article] [PubMed] [Google Scholar]
  14. Starke K., Borowski E., Endo T. Preferential blockade of presynaptic alpha-adrenoceptors by yohimbine. Eur J Pharmacol. 1975 Dec;34(2):385–388. doi: 10.1016/0014-2999(75)90268-x. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Starke K. Presynaptic receptors. Annu Rev Pharmacol Toxicol. 1981;21:7–30. doi: 10.1146/annurev.pa.21.040181.000255. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Stjärne L. Clonidine enhances the secretion of sympathetic neurotransmitter from isolated guineq-pig tissues. Acta Physiol Scand. 1975 Jan;93(1):142–144. doi: 10.1111/j.1748-1716.1975.tb05801.x. [DOI] [PubMed] [Google Scholar]
  19. Story D. F., McCulloch M. W., Rand M. J., Standford-Starr C. A. Conditions required for the inhibitory feedback loop in noradrenergic transmission. Nature. 1981 Sep 3;293(5827):62–65. doi: 10.1038/293062a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES