In vitro studies on 6-fluoronoradrenaline at several peripheral sympathetic neuroeffector junctions
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 words6-Fluoronoradrenaline Sympathetic neurotransmission Neuronal uptake α1- and α2-Adrenoceptors
Unable to display preview. Download preview PDF.
- 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
- Cantacuzene D, Kirk KL, McCulloch DH, Creveling CR (1979) Effect of fluorine substitution on the agonist specificity of norepinephrine. Science 204:1217–1219Google Scholar
- 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
- 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
- Drew GM (1977) Pharmacological characterisation of the presynaptic α-adrenoceptor in the rat vas deferens. Eur J Pharmacol 42:123–130Google Scholar
- 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
- 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
- Iversen LL (1967) The uptake and storage of noradrenaline in sympathetic nerves. Pub Cambridge University PressGoogle Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- Starke K, Borowski E, Endo T (1975b) Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur J Pharmacol 34:385–388Google Scholar