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The heterogeneity of the neuronal distribution of exogenous noradrenaline in the rat vas deferens

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Summary

After loading of the incubated rat vas deferens with 0.2 μmol/l 3H-noradrenaline (followed by 100 min of wash-out with amine-free solution), the efflux of endogenous and exogenous compounds was determined by HPLC with electrochemical detection and by column chromatography with scintillation counting. Two different types of heterogeneity of labelling were found. The first one is due to the preferential labelling of varicosities close to the surface of the tissue, the second one to the preferential labelling of vesicles close to the surface of loaded varicosities. As diffusion distances within the tissue and within varicosities are then longer for endogenous than for exogenous amine and metabolites, the composition of spontaneous efflux of exogenous compounds differed from that for endogenous compounds. Because of preferential neuronal and vesicular re-uptake of endogenous noradrenaline, the percentage contribution by noradrenaline to overall efflux was: endogenous < exogenous. While 3H-DOPEG was the predominant exogenous metabolite, DOPEG and MOPEG equally contributed to the “endogenous” efflux.

Desipramine abolished the consequences of the first heterogeneity of labelling, i.e., it increased the efflux more for endogenous than for exogenous noradrenaline; moreover it decreased the efflux of 3H-DOPEG, but increased that of 3H-MOPEG. The reserpine-like compound Ro 41284, on the other hand, abolished the consequences of the second type of heterogeneity; it reduced the specific activity of “total efflux” (i.e., of the sum of noradrenaline + DOPEG + MOPEG) to the specific activity of the tissue noradrenaline. The degree of heterogeneity of labelling was reduced after inhibition of monoamine oxidase and also when the tissues were loaded with 2 or 20 μmol/l 3H-noradrenaline.

It is proposed that the various “compartments” and “pools” of noradrenaline described in the literature reflect the two heterogeneities described here.

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Abbreviations

COMT:

catechol-O-methyl transferase

DOMA:

dihydroxymandelic acid

DOPEG:

dihydroxyphenylglycol

FRL:

fractional rate of loss (= rate of efflux/tritium content of tissue measured at onset of collection period)

HPLC:

high performance liquid chromatography

MAO:

monoamine oxidase

MOPEG:

methoxyhydroxyphenylglycol

NMN:

normetanephrine

VMA:

vanillylmandelic acid

References

  • Adler-Graschinsky E, Langer SZ, Rubio MC (1972) Metabolism of norepinephrine released by phenoxybenzamine in isolated guinea-pig atria. J Pharmacol Exp Ther 180:286–301

    Google Scholar 

  • Azevedo I, Moura D, Trendelenburg U (1990) Autoradiographic study of the rat vas deferens incubated with 3H-noradrenaline. Naunyn-Schmiedeberg's Arch Pharmacol 342:245–248

    Google Scholar 

  • Bönisch H, Trendelenburg U (1987) Veratridine-induced outward transport of 3H-noradrenaline from adrenergic nerves of the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 336: 621–630

    Google Scholar 

  • Budd GC, Salpeter MM (1969) The distribution of labeled norepinephrine within sympathetic nerve terminals studied with electron microscope radioautography. J Cell Biol 41:21–32

    Google Scholar 

  • Crout JR (1964) The uptake and release of 3H-norepinephrine by the guinea-pig heart in vivo. Naunyn-Schmiedeberg's Arch Pharmacol 248:85–98

    Google Scholar 

  • De la Lande IS, Jellett LB (1972) Relationship between the roles of monoamine oxidase and sympathetic nerves in the vasoconstrictor response of the rabbit ear artery to norepinephrine. J Pharmacol Exp Ther 180:47–55

    Google Scholar 

  • Eisenhofer G, Ropchak TG, Stull RW, Goldstein DS, Keiser HR, Kopin IJ (1987) Dihydroxyphenylglycol and intraneuronal metabolism of endogenous and exogenous norepinephrine in the rat vas deferens. J Pharmacol Exp Ther 241:547–553

    Google Scholar 

  • Eisenhofer G, Ropchak TG, Kopin IJ, Goldstein DS (1988a) Release, metabolism and intraneuronal disposition of exogenous, endogenous and newly synthesized norepinephrine in the rat vas deferens. J Pharmacol Exp Ther 245:81–88

    Google Scholar 

  • Eisenhofer G, Goldstein DS, Ropchak TG, Nguyen HQ, Keiser HR, Kopin IJ (1988b) Source and physiological significance of plasma 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol. J Anton Nerv System 24:1–14

    Google Scholar 

  • Furchgott RF, Sanchez Garcia P (1968) Effects of inhibition of monoamine oxidase on the actions and interactions of norepinephrine, tyramine and other drugs on guinea-pig left atrium. J Pharmacol Exp Ther 163:98–122

    Google Scholar 

  • Graefe K-H, Trendelenburg U (1974) The effect of hydrocortisone on the sensitivity of the isolated nictitating membrane to catecholamines. Relationship to extraneuronal uptake and metabolism. Naunyn-Schmiedeberg's Arch Pharmacol 286:1–48

    Google Scholar 

  • Graefe K-H, Bönisch H, Trendelenburg U (1971) Time-dependent changes in neuronal net uptake of noradrenaline after pretreatment with pargyline and/or reserpine. Naunyn-Schmiedeberg's Arch Pharmacol 271:1–28

    Google Scholar 

  • Graefe K-H, Stefano FJE, Langer SZ (1973) Preferential metabolism of (−)-3H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1160

    Google Scholar 

  • Graefe KH, Stefano FJE, Langer SZ (1977) Stereo selectivity in the metabolism of 3H-noradrenaline during uptake into and efflux from the isolated rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 299:225–238

    Google Scholar 

  • Halbrügge T, Gerhardt T, Ludwig J, Heidbreder E, Graefe K-H (1988) Assay of cateeholamines and dihydroxyphenylethyleneglycol in human plasma and its application in orthostasis and mental stress. Life Sci 43:19–26

    Google Scholar 

  • Halbrügge T, Wölfel R, Graefe K-H (1989) Plasma 3,4-dihydroxyphenylglycol as a tool to assess the role of neuronal uptake in the anaesthetized rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 340:726–732

    Google Scholar 

  • Hughes J (1973) Differential labelling of intraneuronal noradrenaline stores with different concentrations of (−)-3H-noradrenaline. Br J Pharmacol 47:428–430

    Google Scholar 

  • Iversen LL, Langer SZ (1969) Effects of phenoxybenzamine on the uptake and metabolism of noradrenaline in the rat heart and vas deferens. Br J Pharmacol 37:627–637

    Google Scholar 

  • Iversen LL, Salt P, Wilson HA (1972) Inhibition of catecholamine uptake in the isolated rat heart by haloalkylamines related to phenoxybenzamine. Br J Pharmacol 46:647–657

    Google Scholar 

  • Langeloh A, Trendelenburg U (1987) The mechanism of the 3H-noradrenaline releasing effect of various substrates of uptake1: role of monoamine oxidase and of vesicularly stored 3H-noradrenaline. Naunyn-Schmiedeberg's Arch Pharmacol 336: 611–620

    Google Scholar 

  • Langeloh A, Bönisch H, Trendelenburg U (1987) The mechanism of the 3H-noradrenaline releasing effect of various substrates of uptake1: multifactorial induction of outward transport. Naunyn-Schmiedeberg's Arch Pharmacol 336:602–619

    Google Scholar 

  • Lentzen H, Philippu A (1977) Uptake of tyramine into synaptic vesicles of the caudate nucleus. Naunyn-Schmiedeberg's Arch Pharmacol 300:25–30

    Google Scholar 

  • Mack F, Bönisch H (1979) Dissociation constants and lipophilicity of catecholamines and related compounds. Naunyn-Schmiedeberg's Arch Pharmacol 310:1–9

    Google Scholar 

  • Majewski H, Hedler L, Steppeler A, Starke K (1982) Metabolism of endogenous and exogenous noradrenaline in the rabbit perfused heart. Naunyn-Schmiedeberg's Arch Pharmacol 319:125–129

    Google Scholar 

  • Moura D, Azevedo I, Guimaraes S (1990) Differential distribution and differential release of endogenous noradrenaline and recently incorporated amines from sympathetic nerve endings. Naunyn-Schmiedeberg's Arch Pharmacol

  • Niebler M, Trendelenburg U (1990) Mechanisms of release of 3H-noradrenaline by dimethylphenylpiperazinium (DMPP) in the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 341:43–49

    Google Scholar 

  • Schömig E, Trendelenburg U (1987) Simulation of outward transport of neuronal 3H-noradrenaline with the help of a two-compartment model. Naunyn-Schmiedeberg's Arch Pharmacol 336:631–640

    Google Scholar 

  • Schömig E, Fischer P, Schönfeld C-L, Trendelenburg U (1989) The extent of neuronal re-uptake of 3H-noradrenaline in isolated vasa deferentia and atria of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 340:502–508

    Google Scholar 

  • Schönfeld C-L (1990) The spontaneous efflux of endogenous and exogenous noradrenaline (NA) and its main metabolites from the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 341:R83

    Google Scholar 

  • Schönfeld C-L, Trendelenburg U (1989) The release of 3H-noradrenaline by p- and m-tyramines and -octopamines, and the effect of deuterium substitution in α-position. Naunyn-Schmiedeberg's Arch Pharmacol 339:433–440

    Google Scholar 

  • Snedecor GW, Cochran WG (1980) Statistical methods. 7th edn. Iowa State University Press

  • Starke K, Hedler L, Steppeler A (1981) Metabolism of endogenous and exogenous noradrenaline in guinea-pig atria. Naunyn-Schmiedeberg's Arch Pharmacol 317:193–198

    Google Scholar 

  • Stute N, Trendelenburg U (1984) The outward transport of axoplasmic noradrenaline induced by a rise of the sodium concentration in the adrenergic nerve endings of the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 327:124–132

    Google Scholar 

  • TrendelenburgU (1990) Two types of inhomogeneous 3H-noradrenaline (3H-NA) labelling of the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 341:R83

    Google Scholar 

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie der Universität Würzburg, Versbacher Strasse 9, D-8700, Würzburg, Federal Republic of Germany

    E. Schömig, C.-L. Schönfeld, T. Halbrügge, K.-H. Graefe & U. Trendelenburg

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  1. E. Schömig
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  2. C.-L. Schönfeld
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  3. T. Halbrügge
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  4. K.-H. Graefe
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  5. U. Trendelenburg
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Send offprint requests to E. Schömig at the above address

This study was supported by the Deutsche Forschungsgemeinschaft (SFB 176, Gr 490/5 and Scho 383/1). Some of the results were presented to the German Pharmacological Society (Schönfeld 1990; Trendelenburg 1990)

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Schömig, E., Schönfeld, CL., Halbrügge, T. et al. The heterogeneity of the neuronal distribution of exogenous noradrenaline in the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 342, 160–170 (1990). https://doi.org/10.1007/BF00166959

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  • DOI: https://doi.org/10.1007/BF00166959

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