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. 1972 Dec;227(3):647–664. doi: 10.1113/jphysiol.1972.sp010052

Vascular responses and noradrenaline overflows in the isolated blood-perfused cat spleen: some effects of cocaine, normetanephrine and α-blocking agents

Heather Cripps, D P Dearnaley
PMCID: PMC1331280  PMID: 4405551

Abstract

1. Vascular responses and noradrenaline overflows have been studied in the isolated blood-perfused cat spleen in response to electrical stimulation of the splenic nerve with trains of 200 supramaximal pulses at a frequency of 10 Hz given at 10 min intervals.

2. In the absence of blocking agents the spleen gave well-defined responses and a mean maximum overflow of 436 ± 96 pg noradrenaline per stimulus (n = 4) at the third train of stimuli.

3. Cocaine (2 × 10-5 M) increased the response nearly threefold and raised the overflow to 840 ± 131 pg/stim (n = 4). At later stimulations the responses remained stable, but the overflows rose progressively to 1076 ± 51 pg/stim after five trains of stimuli.

4. Normetanephrine (10-4 M) had no significant effect on response, but elevated the overflow to a mean maximum of 868 ± 169 pg/stim (n = 4).

5. Cocaine (2 × 10-5 M) and normetanephrine (10-4 M) given together increased the response by a factor of 6·5 and raised the overflow to 1258 ± 247 pg/stim (n = 4).

6. Hydergine (approx. 10-5 M) almost completely abolished the response and raised the overflow to 859 ± 173 pg/stim (n = 4).

7. Cocaine (2 × 10-5 M), normetanephrine (10-4 M) and hydergine (approx. 10-5 M) given in combination abolished the response and raised the overflow to 4089 ± 1148 pg/stim (n = 4).

8. Phenoxybenzamine (10-4 M) abolished the response and elevated the overflow to 4215 ± 738 pg/stim (n = 4).

9. These results are interpreted in terms of selective and combined block of `uptake I', `uptake II' and α-adrenergic receptors. Facilitation of transmitter release by α-blocking drugs, and the possible existence of an uptake process associated with the α-receptors are discussed.

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Selected References

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

  1. Avakian O. V., Gillespie J. S. Uptake of noradrenaline by adrenergic nerves, smooth muscle and connective tissue in isolated perfused arteries and its correlation with the vasoconstrictor response. Br J Pharmacol Chemother. 1968 Jan;32(1):168–184. doi: 10.1111/j.1476-5381.1968.tb00441.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BLAKELEY A. G., BROWN G. L., FERRY C. B. Pharmacological experiments on the release of the sympathetic transmitter. J Physiol. 1963 Jul;167:505–514. doi: 10.1113/jphysiol.1963.sp007165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Blakeley A. G., Brown L., Dearnaley D. P., Woods R. I. Perfusion of the spleen with blood containing prostaglandin E1: transmitter liberation and uptake. Proc R Soc Lond B Biol Sci. 1969 Dec 23;174(1036):281–292. doi: 10.1098/rspb.1969.0094. [DOI] [PubMed] [Google Scholar]
  6. Blakeley A. G., Brown L., Geffen L. B. Uptake and re-use of sympathetic transmitter in the cat's spleen. Proc R Soc Lond B Biol Sci. 1969 Oct 7;174(1034):51–68. doi: 10.1098/rspb.1969.0080. [DOI] [PubMed] [Google Scholar]
  7. Cripps H., Dearnaley D. P. Evidence suggesting uptake of noradrenaline at adrenergic receptors in the isolated blood-perfused cat spleen. J Physiol. 1971 Jul;216(2):55P–56P. [PubMed] [Google Scholar]
  8. De Potter W. P., Chubb I. W., Put A., De Schaepdryver A. F. Facilitation of the release of noradrenaline and dopamine- -hydroxylase at low stimulation frequencies by -blocking agents. Arch Int Pharmacodyn Ther. 1971 Sep;193(1):191–197. [PubMed] [Google Scholar]
  9. Dearnaley D. P., Geffen L. B. Effect of nerve stimulation on the noradrenaline content of the spleen. Proc R Soc Lond B Biol Sci. 1966 Dec 13;166(1004):303–315. doi: 10.1098/rspb.1966.0101. [DOI] [PubMed] [Google Scholar]
  10. Eisenfeld A. J., Landsberg L., Axelrod J. Effect of drugs on the accumulation and metabolism of extraneuronal norepinephrine in the rat heart. J Pharmacol Exp Ther. 1967 Dec;158(3):378–385. [PubMed] [Google Scholar]
  11. GILLESPIE J. S., KIRPEKAR S. M. THE INACTIVATION OF INFUSED NORADRENALINE BY THE CAT SPLEEN. J Physiol. 1965 Jan;176:205–227. doi: 10.1113/jphysiol.1965.sp007545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. IVERSEN L. L. THE UPTAKE OF NORADRENALINE BY THE ISOLATED PERFUSED RAT HEART. Br J Pharmacol Chemother. 1963 Dec;21:523–537. doi: 10.1111/j.1476-5381.1963.tb02020.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson D. G., Thoa N. B., Weinshilboum R., Axelrod J., Kopin I. J. Enhanced release of dopamine- -hydroxylase from sympathetic nerves by calcium and phenoxybenzamine and its reversal by prostaglandins. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2227–2230. doi: 10.1073/pnas.68.9.2227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kirpekar S. M., Puig M. Effect of flow-stop on noradrenaline release from normal spleens and spleens treated with cocaine, phentolamine or phenoxybenzamine. Br J Pharmacol. 1971 Oct;43(2):359–369. [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Lightman S. L., Iversen L. L. The role of uptake2 in the extraneuronal metabolism of catecholamines in the isolated rat heart. Br J Pharmacol. 1969 Nov;37(3):638–649. doi: 10.1111/j.1476-5381.1969.tb08502.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. THOENEN H., HUERLIMANN A., HAEFELY W. THE EFFECT OF SYMPATHETIC NERVE STIMULATION ON VOLUME, VASCULAR RESISTANCE, AND NOREPINEPHRINE OUTPUT IN THE ISOLATED PERFUSED SPLEEN OF THE CAT, AND ITS MODIFICATION BY COCAINE. J Pharmacol Exp Ther. 1964 Jan;143:57–63. [PubMed] [Google Scholar]
  19. TRENDELENBURG U. The supersensitivity caused by cocaine. J Pharmacol Exp Ther. 1959 Jan;125(1):55–65. [PubMed] [Google Scholar]

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