Metabolism of endogenous and exogenous noradrenaline in the rabbit perfused heart
- 17 Downloads
The outflow of noradrenaline, 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) from rabbit perfused hearts was studied by chromatography on alumina followed by high pressure liquid chromatography with electrochemical detection. In the absence of drugs and without nerve stimulation, the outflow of endogenous noradrenaline over a period of 108 min averaged 0.17 pmol×g−1×min−1 and the outflow of DOPEG 2.1 pmol×g−1×min−1. The outflow of DOMA was below the detection limit (<0.13 pmol×g−1×min−1). The effect of perfusion with (−)-noradrenaline 0.1, 1 or 10 μmol/l for 18 min was then investigated. As the concentration of noradrenaline increased so did the outflow of DOPEG. Moreover, DOMA was found in the venous effluent during and after perfusion with noradrenaline 1 or 10 μmol/l. The increase in the outflow of DOPEG and DOMA was almost abolished when cocaine 10 μmol/l was present during the perfusion with noradrenaline 1 μmol/l. The release of endogenous noradrenaline by sympathetic nerve stimulation or tyramine 10 μmol/l, but not the release evoked by nicotine 30 μmol/l, was accompanied by an increase in the outflow of DOPEG; an outflow of DOMA was not observed.
It is concluded that, in the rabbit perfused heart, DOPEG is an important metabolite of endogenous noradrenaline. DOMA is at best a minor product, either when the neurones are at rest or when noradrenaline is released by sympathetic nerve stimulation, nicotine or tyramine. DOMA is formed in detectable amounts when the tissue is exposed to a high concentration of exogenous noradrenaline. Like DOPEG, it is formed intraneuronally. The results confirm and extend those obtained previously on guinea-pig incubated atria. They make it unlikely that, in these tissues at least, DOMA formation is one of the physiological pathways of noradrenaline catabolism.
Key wordsRabbit heart Noradrenaline metabolism Nicotine Tyramine
Unable to display preview. Download preview PDF.
- Adler-Graschinsky E, Langer SZ, Rubio MC (1972) Metabolism of norepinephrine released by phenoxybenzamine in isolated guineapig atria. J Pharmacol Exp Ther 180:286–301Google Scholar
- Anton AH, Sayre DF (1962) A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther 138:360–375Google Scholar
- Brandão F, Monteiro JG, Osswald W (1978) Differences in the metabolic fate of noradrenaline released by electrical stimulation or by tyramine. Naunyn-Schmiedeberg's Arch Pharmacol 305:37–40Google Scholar
- Graefe KH (1981) The disposition of 3H-(−)-noradrenaline in the perfused cat and rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 318:71–82Google Scholar
- Huković S, Muscholl E (1962) Die Noradrenalin-Abgabe aus dem isolierten Kaninchenherzen bei sympathischer Nervenreizung und ihre pharmakologische Beeinflussung. Naunyn-Schmiedebergs Arch Exp Pathol Pharmakol 244:81–96Google Scholar
- Jayasundar S, Vohra MM (1978) An analysis of action of nictotinic agents on adrenergic nerve terminals in rat isolated vas deferens. Arch Int Pharmacodyn 232:192–201Google Scholar
- Langer SZ (1974) Selective metabolic pathways for noradrenaline in the peripheral and in the central nervous system. Med Biol 52:372–383Google Scholar
- Löffelholz K (1970) Autoinhibition of nicotinic release of noradrenaline from postganglionic sympathetic nerves. Naunyn-Schmiedeberg's Arch Pharmakol 267:49–63Google Scholar
- Muldoon SH, Vanhoutte PM, Tyce GM (1978) Norepinephrine metabolism in canine saphenous vein: prevalence of glycol metabolites. Am J Physiol 234:H235-H243Google Scholar
- Sarantos-Laska C, Majewski H, McCulloch MW, Rand MJ (1980) Mechanism of noradrenaline release from rabbit atria by nicotinic agonists. Arch Int. Pharmacodyn 247:294–305Google Scholar
- Starke K, Weitzell R (1978) Is histamine involved in the sympathomimetic effect of nicotine? Naunyn-Schmiedeberg's Arch Pharmacol 304:237–248Google Scholar
- Starke K, Hedler L, Steppeler A (1981) Metabolism of endogenous and exogenous noradrenaline in guinea-pig atria. Naunyn-Schmiedeberg's Arch Pharmacol 317:193–198Google Scholar
- Steppeler A, Pfändler R, Hedler L, Starke K (1980) An analysis of the effects of amezinium on postganglionic sympathetic neurones. Naunyn-Schmiedeberg's Arch Pharmacol 314:1–11Google Scholar
- Trendelenburg U, Bönisch H, Graefe KH, Henseling M (1980) The rate constants for the efflux of metabolites of catecholamines and phenylethylamines. Pharmacol Rev 31:179–203Google Scholar