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. 1981 Jun;73(2):363–371. doi: 10.1111/j.1476-5381.1981.tb10430.x

The role of calcium in the effects of noradrenaline and phenoxybenzamine on adrenergic transmitter release from atria: no support for negative feedback of release

Stanley Kalsner
PMCID: PMC2071668  PMID: 6113016

Abstract

1 The relation of calcium ion influx into nerve terminals to presynaptic adrenoceptor function and the possible masking, by desensitization due to intraneuronal calcium accumulation, of the effects of adrenoceptor agonists and antagonists on presynaptic α-adrenoceptors was investigated in guinea-pig atria previously incubated with [3H]-noradrenaline.

2 Atria were stimulated with 100 pulses at various frequencies (1 to 15 Hz) in standard (2.3 mm), low (0.26 mm) and high (6.9 mm) calcium-Krebs solution in the absence and then the presence first of noradrenaline and subsequently phenoxybenzamine.

3 The per pulse overflow of tritium was directly related to the calcium concentration of the Krebs solution, being much reduced and substantially increased in 0.26 and 6.9 mm calcium-Krebs solutions respectively.

4 Noradrenaline inhibited the overflow of tritium in low calcium-Krebs solution, to a relatively constant extent, independently of frequency. In addition, the agonist had a greater maximal inhibitory effect in standard than in reduced calcium-Krebs. The catecholamine was as effective an inhibitor of overflow at the lowest and highest frequencies in high as it was in standard calcium-Krebs solution. Phenoxybenzamine invariably increased the tritium overflow but was generally less effective both in low and in high calcium-Krebs solution. The patterns of inhibition and enhancement of stimulation-induced tritium overflow by these two agents do not indicate an intimate relationship between calcium influx and adrenoceptor activation; nor does desensitization appear to be an adequate explanation of the relationship between frequency of stimulation and the intensity of agonist and antagonist effect in the three different calcium concentrations.

5 It is concluded that the perineuronal levels of adrenergic transmitter do not establish the magnitudes of effect of exogenous adrenoceptor agonists and antagonists on tritium overflow and that a negative feedback regulation of release by transmitter is exceedingly unlikely under ordinary conditions of neurotransmission.

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Selected References

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

  1. Blaustein M. P., Ratzlaff R. W., Kendrick N. K. The regulation of intracellular calcium in presynaptic nerve terminals. Ann N Y Acad Sci. 1978 Apr 28;307:195–212. doi: 10.1111/j.1749-6632.1978.tb41943.x. [DOI] [PubMed] [Google Scholar]
  2. Chan C. C., Kalsner S. An examination of the negative feedback function of presynaptic adrenoceptors in a vascular tissue. Br J Pharmacol. 1979 Nov;67(3):401–407. doi: 10.1111/j.1476-5381.1979.tb08694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chan C. C., Kalsner S. Noradrenaline inhibition of transmitter efflux in a renal artery preparation and the presynaptic receptor theory. Can J Physiol Pharmacol. 1979 Oct;57(10):1192–1195. doi: 10.1139/y79-179. [DOI] [PubMed] [Google Scholar]
  4. Drew G. M. The effect of different calcium concentrations on the inhibitory effect of presynaptic alpha-adrenoceptors in the rat vas deferens. Br J Pharmacol. 1978 Jul;63(3):417–419. doi: 10.1111/j.1476-5381.1978.tb07792.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Furchgott R. F., Garcia P. S., Wakade A. R., Cervoni P. Interactions of bretylium and other drugs on guinea-pig atria: evidence for inhibition of neuronal monoamine oxidase by bretylium. J Pharmacol Exp Ther. 1971 Nov;179(2):171–185. [PubMed] [Google Scholar]
  6. Furchgott R. F., Sanchez Garcia P. Effects of inhibition of monoamine oxidase on the actions and interactions of norepinephrine, tyramine and other drugs on guinea-pig left atrium. J Pharmacol Exp Ther. 1968 Sep;163(1):98–122. [PubMed] [Google Scholar]
  7. 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]
  8. Kalsner S. Adrenergic presynaptic receptors: examination of a hypothesis in guinea pig vas deferens. Can J Physiol Pharmacol. 1979 Jul;57(7):717–724. doi: 10.1139/y79-108. [DOI] [PubMed] [Google Scholar]
  9. Kalsner S., Chan C. C. Adrenergic antagonists and the presynaptic receptor hypothesis in vascular tissue. J Pharmacol Exp Ther. 1979 Nov;211(2):257–264. [PubMed] [Google Scholar]
  10. Kalsner S., Chan C. C. Inhibition by dopamine of the stimulation-induced efflux of [3H]noradrenaline in renal arteries: limitations of the unitary hypothesis of presynaptic regulation of transmitter release. Can J Physiol Pharmacol. 1980 May;58(5):504–512. doi: 10.1139/y80-084. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Kalsner S., Suleiman M., Dobson R. E. Adrenergic presynaptic recpetors: an overextended hypothesis? J Pharm Pharmacol. 1980 Apr;32(4):290–292. doi: 10.1111/j.2042-7158.1980.tb12914.x. [DOI] [PubMed] [Google Scholar]
  14. Kalsner S. The effects of (+)- and (-)-propranolol on 3H-transmitter efflux in guinea-pig atria and the presynaptic beta-adrenoceptor hypothesis. Br J Pharmacol. 1980 Nov;70(3):491–498. doi: 10.1111/j.1476-5381.1980.tb08728.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Langer S. Z. Sixth gaddum memorial lecture, National Institute for Medical Research, Mill Hill, January 1977. Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol. 1977 Aug;60(4):481–497. doi: 10.1111/j.1476-5381.1977.tb07526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Marshall I., Nasmyth P. A., Shepperson N. B. The relationship between pre-synaptic alpha-adrenoceptors, stimulation frequency and calcium [proceedings]. Br J Pharmacol. 1977 Sep;61(1):128P–128P. [PMC free article] [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. 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]
  19. Younkin S. G. An analysis of the role of calcium in facilitation at the frog neuromuscular junction. J Physiol. 1974 Feb;237(1):1–14. doi: 10.1113/jphysiol.1974.sp010466. [DOI] [PMC free article] [PubMed] [Google Scholar]

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