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. 1974 Mar;237(3):505–519. doi: 10.1113/jphysiol.1974.sp010495

Negative feedback 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

Margarita L Dubocovich, S Z Langer
PMCID: PMC1350902  PMID: 4363457

Abstract

1. The effects of low concentrations of phenoxybenzamine (8·8 × 10-10 to 2·9 × 10-7 M) on responses and on noradrenaline overflow elicited by nerve stimulation were studied in the perfused cat's spleen.

2. In the presence of 8·8 × 10-10 M or 2·9 × 10-9 M phenoxybenzamine there was a significant reduction in responses to nerve stimulation while the overflow of the transmitter did not increase at the two frequencies of stimulation employed: 5 and 30 Hz.

3. In the presence of 2·9 × 10-8 M or 2·9 × 10-7 M phenoxybenzamine the responses to nerve stimulation were practically abolished and a significant increase in transmitter overflow was obtained at both frequencies of stimulation. The drug was more effective in increasing transmitter overflow at 5 Hz when compared with 30 Hz.

4. The higher effectiveness of phenoxybenzamine in blocking the post-synaptic α-receptor when compared with the blockade of the presynaptic α-receptor that regulates transmitter release is compatible with the view that these two receptors are not identical.

5. A second alternative for the difference in effectiveness of phenoxybenzamine is that both types of α receptors are identical, but the spare receptor capacity for the presynaptic adrenergic receptors is higher than that of the post-synaptic receptors.

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Selected References

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

  1. Armstrong J. M., Boura A. L. Effects of clonidine and guanethidine on peripheral sympathetic nerve function in the pithed rat. Br J Pharmacol. 1973 Apr;47(4):850–852. doi: 10.1111/j.1476-5381.1973.tb08214.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BROWN G. L., DAVIES B. N., FERRY C. B. The effect of neuronal rest on the output of sympathetic transmitter from the spleen. J Physiol. 1961 Dec;159:365–380. doi: 10.1113/jphysiol.1961.sp006814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BROWN G. L., GILLESPIE J. S. The output of sympathetic transmitter from the spleen of the cat. J Physiol. 1957 Aug 29;138(1):81–102. doi: 10.1113/jphysiol.1957.sp005839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bennett M. R. An electrophysiological analysis of the uptake of noradrenaline at sympathetic nerve terminals. J Physiol. 1973 Mar;229(2):533–546. doi: 10.1113/jphysiol.1973.sp010152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boullin D. J., Costa E., Brodie B. B. Apparent depletion of NE stores after repetitive stimulation of cat colon in presence of phenoxybenzamine. Int J Neuropharmacol. 1966 Jul;5(4):293–298. doi: 10.1016/0028-3908(66)90037-2. [DOI] [PubMed] [Google Scholar]
  6. Boullin D. J., Costa E., Brodie B. B. Evidence that blockade of adrenergic receptors causes overflow of norepinephrine in cats colon after nerve stimulation. J Pharmacol Exp Ther. 1967 Jul;157(1):125–134. [PubMed] [Google Scholar]
  7. 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]
  8. Enero M. A., Langer S. Z., Rothlin R. P., Stefano F. J. Role of the -adrenoceptor in regulating noradrenaline overflow by nerve stimulation. Br J Pharmacol. 1972 Apr;44(4):672–688. doi: 10.1111/j.1476-5381.1972.tb07306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Farnebo L. O., Hamberger B. Drug-induced changes in the release of ( 3 H)-noradrenaline from field stimulated rat iris. Br J Pharmacol. 1971 Sep;43(1):97–106. doi: 10.1111/j.1476-5381.1971.tb07160.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Gillespie J. S., Hamilton D. N., Hosie J. A. The extraneuronal uptake and localization of noradrenaline in the cat spleen and the effect on this of some drugs, of cold and of denervation. J Physiol. 1970 Mar;206(3):563–590. doi: 10.1113/jphysiol.1970.sp009031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gillespie J. S., Kirpekar S. M. The uptake and release of radioactive noradrenaline by the splenic nerves of cats. J Physiol. 1966 Nov;187(1):51–68. doi: 10.1113/jphysiol.1966.sp008075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Haefely W., Hürlimann A., Thoenen H. Relation between the rate of stimulation and the quantity of noradrenaline liberated from sympathetic nerve endings in the isolated perfused spleen of the cat. J Physiol. 1965 Nov;181(1):48–58. doi: 10.1113/jphysiol.1965.sp007744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Häggendal J., Johansson B., Jonason J., Ljung B. Effects of phenoxybenzamine on transmitter release and effector response in the isolated portal vein. J Pharm Pharmacol. 1972 Feb;24(2):161–164. doi: 10.1111/j.2042-7158.1972.tb08954.x. [DOI] [PubMed] [Google Scholar]
  15. Langer S. Z. The metabolism of (3H)noradrenaline released by electrical stimulation from the isolated nictitating membrane of the cat and from the vas deferens of the rat. J Physiol. 1970 Jul;208(3):515–546. doi: 10.1113/jphysiol.1970.sp009135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Langer S. Z., Trendelenburg U. Decrease in effectiveness of phenoxybenzamine after chronic denervation and chronic decentralization of the nictitating membrane of the pithed cat. J Pharmacol Exp Ther. 1968 Oct;163(2):290–299. [PubMed] [Google Scholar]
  17. Langer S. Z., Vogt M. Noradrenaline release from isolated muscles of the nictitating membrane of the cat. J Physiol. 1971 Apr;214(1):159–171. doi: 10.1113/jphysiol.1971.sp009425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laverty R., Taylor K. M. The fluorometric assay of catecholamines and related compounds: improvements and extensions to the hydroxyindole technique. Anal Biochem. 1968 Feb;22(2):269–279. doi: 10.1016/0003-2697(68)90316-3. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Starke K., Montel H., Schümann H. J. Influence of cocaine and phenoxybenzamine on noradrenaline uptake and release. Naunyn Schmiedebergs Arch Pharmakol. 1971;270(2):210–214. doi: 10.1007/BF00997091. [DOI] [PubMed] [Google Scholar]
  22. THOENEN H., HUERLIMANN A., HAEFELY W. REMOVAL OF INFUSED NOREPINEPHRINE BY THE CAT'S SPLEEN; MECHANISM OF ITS INHIBITION BY PHENOXYBENZAMINE. Experientia. 1963 Nov 15;19:601–602. doi: 10.1007/BF02151014. [DOI] [PubMed] [Google Scholar]
  23. THOENEN H., HUERLIMANN A., HAEFELY W. WIRKUNGEN VON PHENOXYBENZAMIN, PHENTOLAMIN UND AZAPETIN AUF ADRENERGISCHE SYNAPSEN DER KATZENMILZ. BLOCKIERUNG DER ALPHA-ADRENERGISCHEN REZEPTOREN UND HEMMUNG DER WIEDERAUFNAHME VON NEURAL FREIGESETZTEM NORADRENALIN. Helv Physiol Pharmacol Acta. 1964;22:148–161. [PubMed] [Google Scholar]
  24. Thoenen H., Hürlimann A., Haefely W. Dual site of action of phenoxybenzamine in the cat's spleen; blockade of alpha-adrenergic receptors and inhibition of re-uptake of neurally released norepinephrine. Experientia. 1964 May 15;20(5):272–273. doi: 10.1007/BF02151802. [DOI] [PubMed] [Google Scholar]
  25. Waud D. R. On the estimation of receptor occlusion by irreversible competitive pharmacological antagonists. Biochem Pharmacol. 1968 May;17(5):649–653. doi: 10.1016/0006-2952(68)90001-4. [DOI] [PubMed] [Google Scholar]
  26. Zimmerman B. G., Liao J. C., Gisslen J. Effect of phenoxybenzamine and combined administration of iproniazid and tropolone on catecholamine release elicited by renal sympathetic nerve stimulation. J Pharmacol Exp Ther. 1971 Mar;176(3):603–610. [PubMed] [Google Scholar]

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