In vitro studies on 6-fluoronoradrenaline at several peripheral sympathetic neuroeffector junctions

  • N. B. Shepperson
  • T. Purcell
  • R. Massingham
  • S. Z. Langer


A comparison of the effects of noradrenaline and 6-fluoronoradrenaline has been made at several peripheral sympathetic neuroeffector junctions. In the rat vas deferens preparation in the presence of 1 μM cocaine, 6-fluoronor-adrenaline was found to be about 9 times more potent than noradrenaline as an agonist at presynaptic inhibitory α2-adrenoceptors. In the rabbit aorta, 6-fluoronoradrenaline had approximately one tenth of the potency of noradrenaline in stimulating the postsynaptic α1-adrenoceptors. Furthermore 6-fluoronoradrenaline, in contrast to previous reports, appears to be a substrate for the neuronal uptake process since exposure to cocaine potentiated the inhibition of the twitch response of the vas deferens by 6-fluoronoradrenaline. In addition, 6-fluoronoradrenaline increased the spontaneous outflow of radioactivity from rabbit pulmonary artery strips prelabelled with 3H-noradrenaline and this increase was blocked by cocaine (30μM).

These results demonstrate that 6-fluoronoradrenaline is a preferential α2-adrenoceptor agonist which is a substrate for the neuronal uptake process in peripheral sympathetically innervated smooth muscle preparations.

Key words

6-Fluoronoradrenaline Sympathetic neurotransmission Neuronal uptake α1- and α2-Adrenoceptors 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arnold A (1980) Sympathomimetic amine-induced responses of effecton organs subserved by alpha, beta1-and beta2-adrenoceptors. In: Szekeres L (ed) Adrenergic activators and inhibitors. Part 1. Springer, Berlin Heidelberg New York, pp 63–88Google Scholar
  2. Cantacuzene D, Kirk KL, McCulloch DH, Creveling CR (1979) Effect of fluorine substitution on the agonist specificity of norepinephrine. Science 204:1217–1219Google Scholar
  3. Daly JW, Padgett W, Nimitkitpaisan Y, Creveling CR, Cantacuzene D, Kirk KL (1980) Fluoronorepinephrines: specific agonists for the activation of alpha and beta-adrenergic-sensitive cyclic AMP-generating systems in brain slices. J Pharmacol Exp Ther 212:382–389Google Scholar
  4. Docherty JR, Starke K (in press) An examination of postsynaptic α-adrenoceptor subtypes in rabbit blood vessels and rat anococcygeus muscle in vitro. J Cardiovasc PharmacolGoogle Scholar
  5. Drew GM (1977) Pharmacological characterisation of the presynaptic α-adrenoceptor in the rat vas deferens. Eur J Pharmacol 42:123–130Google Scholar
  6. Graefe KH, Trendelenburg U (1974) The effect of hydrocortisone on the sensitivity of the isolated nictitating membrane to catecholamines. Naunyn-Schmiedeberg's Arch Pharmacol 286:1–48Google Scholar
  7. Graefe KH, Stefano FJE, Langer SZ (1973) Preferential metabolism of (−)norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1161Google Scholar
  8. Iversen LL (1967) The uptake and storage of noradrenaline in sympathetic nerves. Pub Cambridge University PressGoogle Scholar
  9. Kirk KL, Cantacuzene D, Nimitkitpaisan Y, McCulloh D, Padgett WL, Daly JW, Creveling CR (1979) Synthesis and biological properties of 2-, 5-and 6-fluoronorepinephrines. J Med Chem 22:1493–1497Google Scholar
  10. Langer SZ (1973) The regulation of transmitter release elicited by nerve stimulation through a presynaptic feed-back mechanism. In: Usdin E, Snyder S (eds) Frontiers in catecholamines research. Pergamon Press, Inc. Oxford New York, pp 543–549Google Scholar
  11. Langer SZ (1979) Presynaptic receptors and the regulation of transmitter release in the peripheral and central nervous system: physiological and pharmacological significance. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: basic and clinical frontiers, vol 1. Pergamon Press, New York, pp 387–398Google Scholar
  12. Langer SZ, Dubocovich ML, Celuch SM (1975) Prejunctional regulatory mechanism for noradrenaline release elicited by nerve stimulation. In: Algren O, Carlsson A, Engel J (eds) Chemical tools in catecholamine research II. North Holland/American Elsevier. New York, pp 183–191Google Scholar
  13. Rand MJ, McCulloch MW, Story DF (1980) Catecholamine receptors on nerve terminals. In: Szekeres L (ed) Adrenergic activators and inhibitors Part I. Springer, Berlin Heidelberg New York, pp 223–266Google Scholar
  14. Starke K, Endo T, Taube HD (1975a) Relative pre-and postsynaptic potencies of α-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 291:55–78Google Scholar
  15. Starke K, Borowski E, Endo T (1975b) Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur J Pharmacol 34:385–388Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • N. B. Shepperson
    • 1
  • T. Purcell
    • 2
  • R. Massingham
    • 1
  • S. Z. Langer
    • 1
  1. 1.Department of BiologyLaboratoires d'Etudes et de Recherches SynthélaboParisFrance
  2. 2.Department of ChemistryLaboratoires d'Etudes et de Recherches SynthélaboParisFrance

Personalised recommendations