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. 1971 Mar;41(3):462–479. doi: 10.1111/j.1476-5381.1971.tb08044.x

Actions of noradrenaline, other sympathomimetic amines and antagonists on neurones in the brain stem of the cat

R J Boakes, P B Bradley, N Brookes, J M Candy, J H Wolstencroft
PMCID: PMC1702877  PMID: 5576254

Abstract

1. The effects of (-)-noradrenaline ((-)-NA) and related compounds on brain stem neurones in decerebrate unanaesthetized cats have been investigated using the technique of iontophoretic application from micropipettes.

2. Four types of response to (-)-NA have been described. These were short lasting inhibition, long lasting inhibition, excitation, and a biphasic response consisting of short lasting inhibition followed by excitation. A variable amount of desensitization of the excitatory response, but not of inhibitory responses, was observed.

3. Experiments in which small currents were used to pass (-)-NA from pipettes with smaller tips did not lead to any appreciable change in the proportions of neurones excited or inhibited.

4. A variety of sympathomimetic agonists was tested. Short lasting inhibition was less sensitive than excitation to changes in molecular structure. Long lasting inhibition was more sensitive to molecular change and was not mimicked by some of the agonists which mimicked short lasting inhibition.

5. Although agonists without one ring hydroxyl had weaker effects than those with both, compounds in which both ring hydroxyl groups were absent (β-hydroxyphenylethylamine, ephedrine and amphetamine) mimicked excitation strongly. It is possible that the compounds without both ring hydroxyl groups had some effect other than simple agonistic activity.

6. A dissociation was observed between responses to dopamine and (-)-NA. p-Tyramine mimicked dopamine, rather than (-)-NA.

7. Neither the α-agonist, phenylephrine nor the β-agonist, isoprenaline mimicked neuronal responses to (-)-NA. The α-antagonists phentolamine and phenoxybenzamine and the β-antagonists dichloroisoprenaline, propranolol and D(-)-INPEA and combinations of propranolol with phentolamine or phenoxybenzamine were ineffective in blocking either excitation or inhibition. Thus, the central receptors appear to be different from peripheral α- and β-receptors.

8. The most effective antagonist of excitation was (-)-α-methylnoradrenaline. Metaraminol and dihydroergotamine also had some antagonistic activity. None of the compounds tested blocked inhibition. The effects of (-)-α-methylnoradrenaline have been discussed in relation to the hypotensive action of α-methyldopa.

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Selected References

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

  1. Aghajanian G. K., Bloom F. E. Electron-microscopic autoradiography of rat hypothalamus after intraventricular h3-norepinephrine. Science. 1966 Jul 15;153(3733):308–310. doi: 10.1126/science.153.3733.308. [DOI] [PubMed] [Google Scholar]
  2. Andén N. E., Dahlström A., Fuxe K., Olson L., Ungerstedt U. Ascending noradrenaline neurons from the pons and the medulla oblongata. Experientia. 1966 Jan 15;22(1):44–45. doi: 10.1007/BF01897761. [DOI] [PubMed] [Google Scholar]
  3. Avanzino G. L., Bradley P. B., Wolstencroft J. H. Pharmacological properties of neurons of the paramedian reticular nucleus. Experientia. 1966 Jun 15;22(6):410–410. doi: 10.1007/BF01901170. [DOI] [PubMed] [Google Scholar]
  4. BAUST W., NIEMCZYK H. FURTHER STUDIES ON THE ACTION OF ADRENERGIC DRUGS ON CORTICAL ACTIVITY. Electroencephalogr Clin Neurophysiol. 1964 Sep;17:261–271. doi: 10.1016/0013-4694(64)90127-0. [DOI] [PubMed] [Google Scholar]
  5. BONVALLET M., DELL P., HIEBEL G. Tonus sympathique et activité électrique corticale. Electroencephalogr Clin Neurophysiol. 1954 Feb;6(1):119–144. doi: 10.1016/0013-4694(54)90011-5. [DOI] [PubMed] [Google Scholar]
  6. BONVALLET M., DELL P., HUGELIN A. Influence de l'adrénaline sur le contrôle réticulaire des activités corticale et spinale. J Physiol (Paris) 1954;46(1):262–265. [PubMed] [Google Scholar]
  7. BRADLEY P. B., WOLSTENCROFT J. H. ACTIONS OF DRUGS ON SINGLE NEURONES IN THE BRAIN-STEM. Br Med Bull. 1965 Jan;21:15–18. doi: 10.1093/oxfordjournals.bmb.a070349. [DOI] [PubMed] [Google Scholar]
  8. BRADLEY P. B., WOLSTENCROFT J. H. Excitaion and inhibition of brain-stem neurones by noradrenaline and acetylcholine. Nature. 1962 Dec 1;196:840–passim. doi: 10.1038/196840a0. [DOI] [PubMed] [Google Scholar]
  9. Biscoe T. J., Curtis D. R., Ryall R. W. An investigation of catecholamine receptors of spinal interneurones. Int J Neuropharmacol. 1966 Nov;5(6):429–434. doi: 10.1016/0028-3908(66)90008-6. [DOI] [PubMed] [Google Scholar]
  10. Boakes R. J., Bradley P. B., Briggs I., Dray A. Antagonism of 5-hydroxytryptamine by LSD 25 in the central nervous system: a possible neuronal basis for the actions of LSD 25. Br J Pharmacol. 1970 Oct;40(2):202–218. doi: 10.1111/j.1476-5381.1970.tb09914.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Boakes R. J., Bradley P. B., Candy J. M. Abolition of the response of brain stem neurones to iontophoretically applied d-amphetamine by reserpine. Nature. 1971 Feb 12;229(5285):496–497. doi: 10.1038/229496a0. [DOI] [PubMed] [Google Scholar]
  12. Boakes R. J., Candy J. M., Wolstencroft J. H. Agonistic and antagonistic effects of alpha-methylnoradrenaline at central receptors. Brain Res. 1968 Nov;11(2):450–452. doi: 10.1016/0006-8993(68)90038-3. [DOI] [PubMed] [Google Scholar]
  13. Bradley P. B., Candy J. M. Iontophoretic release of acetylcholine, noradrenaline, 5-hydroxytryptamine and D-lysergic acid diethylamide from micropipettes. Br J Pharmacol. 1970 Oct;40(2):194–201. doi: 10.1111/j.1476-5381.1970.tb09913.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Bradley P. B., Dhawan B. N., Wolstencroft J. H. Pharmacological properties of cholinoceptive neurones in the medulla and pons of the cat. J Physiol. 1966 Apr;183(3):658–674. doi: 10.1113/jphysiol.1966.sp007891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Bradley P. B. Synaptic transmission in the central nervous system and its relevance for drug action. Int Rev Neurobiol. 1968;11:1–56. doi: 10.1016/s0074-7742(08)60383-9. [DOI] [PubMed] [Google Scholar]
  16. CARLSSON A., LINDQVIST M. In-vivo decarboxylation of alpha-methyl DOPA and alpha-methyl metatyrosine. Acta Physiol Scand. 1962 Jan;54:87–94. doi: 10.1111/j.1748-1716.1962.tb02331.x. [DOI] [PubMed] [Google Scholar]
  17. Collins G. G., West G. B. The release of 3H-dopamine from the isolated rabbit ileum. Br J Pharmacol. 1968 Nov;34(3):514–522. doi: 10.1111/j.1476-5381.1968.tb08480.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Curtis D. R., Crawford J. M. Central synaptic transmission--microelectrophoretic studies. Annu Rev Pharmacol. 1969;9:209–240. doi: 10.1146/annurev.pa.09.040169.001233. [DOI] [PubMed] [Google Scholar]
  19. DAY M. D., RAND M. J. A hypothesis for the mode of action of alpha-methyldopa in relieving hypertension. J Pharm Pharmacol. 1963 Apr;15:221–224. doi: 10.1111/j.2042-7158.1963.tb12778.x. [DOI] [PubMed] [Google Scholar]
  20. Dewhurst S. G. New theory of cerebral amine function and its clinical application. Nature. 1968 Jun 22;218(5147):1130–1133. doi: 10.1038/2181130a0. [DOI] [PubMed] [Google Scholar]
  21. Engberg I., Ryall R. W. The inhibitory action of noradrenaline and other monoamines on spinal neurones. J Physiol. 1966 Jul;185(2):298–322. doi: 10.1113/jphysiol.1966.sp007988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. FELDBERG W., SHERWOOD S. L. Injections of drugs into the lateral ventricle of the cat. J Physiol. 1954 Jan;123(1):148–167. doi: 10.1113/jphysiol.1954.sp005040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. FUXE K. EVIDENCE FOR THE EXISTENCE OF MONOAMINE NEURONS IN THE CENTRAL NERVOUS SYSTEM. IV. DISTRIBUTION OF MONOAMINE NERVE TERMINALS IN THE CENTRAL NERVOUS SYSTEM. Acta Physiol Scand Suppl. 1965:SUPPL 247–247:37+. [PubMed] [Google Scholar]
  24. HERTTING G., AXELROD J. Fate of tritiated noradrenaline at the sympathetic nerve-endings. Nature. 1961 Oct 14;192:172–173. doi: 10.1038/192172a0. [DOI] [PubMed] [Google Scholar]
  25. Haefely W., Hürlimann A., Thoenen H. Adrenergic transmitter changes and response to sympathetic nerve stimulation after differing pretreatment with alpha-methyldopa. Br J Pharmacol Chemother. 1967 Sep;31(1):105–119. doi: 10.1111/j.1476-5381.1967.tb01981.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hebb C. CNS at the cellular level: identity of transmitter agents. Annu Rev Physiol. 1970;32:165–192. doi: 10.1146/annurev.ph.32.030170.001121. [DOI] [PubMed] [Google Scholar]
  27. Hoffer B. J., Siggins G. R., Bloom F. E. Prostaglandins E1 and E2 antagonize norepinephrine effects on cerebellar purkinje cells: microelectrophoretic study. Science. 1969 Dec 12;166(3911):1418–1420. doi: 10.1126/science.166.3911.1418. [DOI] [PubMed] [Google Scholar]
  28. Johnson E. S., Roberts M. H., Sobieszek A., Straughan D. W. Noradrenaline sensitive cells in cat cerebral cortex. Int J Neuropharmacol. 1969 Dec;8(6):549–566. doi: 10.1016/0028-3908(69)90072-0. [DOI] [PubMed] [Google Scholar]
  29. KEY B. J., MARLEY D. E. The effect of the sympathomimetic amines on behaviour and electrocortical activity of the chicken. Electroencephalogr Clin Neurophysiol. 1962 Feb;14:90–105. doi: 10.1016/0013-4694(62)90011-1. [DOI] [PubMed] [Google Scholar]
  30. KRNJEVIC K., PHILLIS J. W. Iontophoretic studies of neurones in the mammalian cerebral cortex. J Physiol. 1963 Feb;165:274–304. doi: 10.1113/jphysiol.1963.sp007057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kopin I. J. False adrenergic transmitters. Annu Rev Pharmacol. 1968;8:377–394. doi: 10.1146/annurev.pa.08.040168.002113. [DOI] [PubMed] [Google Scholar]
  32. Margules D. L. Noradrenergic synapses for the suppression of feeding behavior. Life Sci. 1969 Jul 1;8(13):693–704. doi: 10.1016/0024-3205(69)90258-6. [DOI] [PubMed] [Google Scholar]
  33. Marley E. Behavioural and electrophysiological effects of catecholamines. Pharmacol Rev. 1966 Mar;18(1):753–768. [PubMed] [Google Scholar]
  34. Marley E., Stephenson J. D. Effects of some catecholamines infused into the hypothalamus of young chickens. Br J Pharmacol. 1969 May;36(1):194P–195P. [PMC free article] [PubMed] [Google Scholar]
  35. Phillis J. W., Tebecis A. K. The responses of thalamic neurons to iontophoretically applied monoamines. J Physiol. 1967 Oct;192(3):715–745. doi: 10.1113/jphysiol.1967.sp008327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Phillis J. W., Tebecis A. K., York D. H. Histamine and some antihistamines: their actions on cerebral cortical neurones. Br J Pharmacol Chemother. 1968 Jul;33(3):426–440. doi: 10.1111/j.1476-5381.1968.tb00492.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Roberts M. H., Straughan D. W. Excitation and depression of cortical neurones by 5-hydroxytryptamine. J Physiol. 1967 Nov;193(2):269–294. doi: 10.1113/jphysiol.1967.sp008357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tebecis A. K. Properties of cholinoceptive neurones in the medial geniculate nucleus. Br J Pharmacol. 1970 Jan;38(1):117–137. doi: 10.1111/j.1476-5381.1970.tb10341.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. VOGT M. The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs. J Physiol. 1954 Mar 29;123(3):451–481. doi: 10.1113/jphysiol.1954.sp005064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. WOLFE D. E., POTTER L. T., RICHARDSON K. C., AXELROD J. Localizing tritiated norepinephrine in sympathetic axons by electron microscopic autoradiography. Science. 1962 Oct 19;138(3538):440–442. doi: 10.1126/science.138.3538.440. [DOI] [PubMed] [Google Scholar]
  41. Weight F. F., Salmoiraghi G. C. Responses of spinal cord interneurons to acetylcholine, norepinephrine and serotonin administered by microelectrophoresis. J Pharmacol Exp Ther. 1966 Sep;153(3):420–427. [PubMed] [Google Scholar]
  42. Yamamoto C. Pharmacologic studies of norepinephrine, acetylcholine and related compounds on neurons in Deiters' nucleus and the cerebellum. J Pharmacol Exp Ther. 1967 Apr;156(1):39–47. [PubMed] [Google Scholar]

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