Skip to main content
Log in

The role of neuronal and extraneuronal uptake in the inactivation of 3H-(−)noradrenaline in the rabbit aorta determined by a method relating uptake with amine diffusion in the tissue

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

  1. 1.

    Apparent coefficients of diffusion for 3H-noradrenaline and 14C-sorbitol were determined in the different layers of the rabbit aorta; uptake1 and uptake2 were inhibited. For 3H-noradrenaline, a value of 6.3·10−7 cm2·s−1 was obtained in intact aorta and a similar one in intima-media, while that in adventitia was three times higher than in intact aorta. The apparent coefficient was the same for 3H-noradrenaline and 14C-sorbitol in adventitia. However, the values were slightly higher for 3H-noradrenaline than for 14C-sorbitol in intact aorta and in intima-media. Thus, the distribution of sorbitol did not exactly reflect the distribution of noradrenaline in these two preparations, even when both uptake mechanisms were inhibited.

  2. 2.

    When either uptake1 or uptake2 was intact, about 60% of the 3H-noradrenaline (0.12 μmol·l−1) was inactivated on its way through the vessel wall (intact aorta). This indicated that each mechanism was equieffective in removing noradrenaline from the extracellular fluid either in the adventitia (uptake1) or intima-media (uptake2). Similarly, when noradrenaline left the extracellular space by diffusion, about the same amount of noradrenaline was inactivated neuronally and extraneuronally.

  3. 3.

    However, under classical incubation conditions, neuronal inactivation of 3H-noradrenaline was three to five times higher than extraneuronal one. This difference reflected the rapid access of noradrenaline to the neurones rather than the capacity of the neuronal and extraneuronal uptake sites to remove the amine from the extracellular fluid in the different layers of the aortic wall.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bevan JA, Török MD (1970) Movement of norepinephrine through the media of rabbit aorta. Circ Res 27:325–331

    Google Scholar 

  • Bönisch H (1978) Further studies on the extraneuronal uptake and metabolism of isoprenaline in the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 303:121–131

    Google Scholar 

  • Branco D, Azevedo I, Sarmento A, Osswald W (1981) The fate of isoprenaline in the isolated rabbit aorta. Radiochemical and morphologic observations. Naunyn-Schmiedeberg's Arch Pharmacol 316:120–125

    Google Scholar 

  • Cornish EJ, Goldie RG, Miller RC (1978) Catecholamine uptake by isolated coronary arteries and atria of the kitten. Br J Pharmacol 63:445–456

    Google Scholar 

  • Ebner F, Waud DR (1978) The role of uptake of noradrenaline for its positive inotropic effect in relation to muscle geometry. Naunyn-Schmiedeberg's Arch Pharmacol 303:1–6

    Google Scholar 

  • Garland LG, Marrion NV, Martin GR (1981) The extraneuronal O-methylation of 3H-(±)isoprenaline by guinea-pig tracheal rings in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 318:88–93

    Google Scholar 

  • Graefe K-H, Bönisch H, Keller B (1978) Saturation kinetics of the adrenergic uptake system in the perfused rabbit heart. A new method for the determination of initial rates of amine uptake. Naunyn-Schmiedeberg's Arch Pharmacol 302:263–273

    Google Scholar 

  • Green AL (1976) The kinetics of enzyme action and inhibition in intact tissues and tissue slices, with special reference to cholinesterase. J Pharm Pharmacol 28:265–274

    Google Scholar 

  • Henseling M (1983a) Kinetic constants for uptake and metabolism of 3H-(−)noradrenaline in rabbit aorta. Possible falsification of the constants by diffusion barriers within the vessel wall. Naunyn-Schmiedeberg's Arch Pharmacol 323:12–23

    Google Scholar 

  • Henseling M (1983b) The influence of uptake2 on the inhibition by unlabelled noradrenaline of the stimulation-evoked overflow of 3H-noradrenaline in rabbit aorta with regard to surface of amine entry. Naunyn-Schmiedeberg's Arch Pharmacol 324:99–107

    Google Scholar 

  • Henseling M, Trendelenburg U (1978) Stereoselectivity of the accumulation and metabolism of noradrenaline in rabbit aortic strips. Naunyn-Schmiedeberg's Arch Pharmacol 302:195–206

    Google Scholar 

  • Henseling M, Eckert E, Trendelenburg U (1976) The distribution of 3H-(±)noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes. Naunyn-Schmiedeberg's Arch Pharmacol 292:205–217

    Google Scholar 

  • Henseling M, Rechtsteiner D, Trendelenburg U (1978) The influence of monoamine oxidase and catechol-O-methyl transferase on the distribution of 3H-(±)-noradrenaline in rabbit aortic strips. Naunyn-Schmiedeberg's Arch Pharmacol 302:181–194

    Google Scholar 

  • Kalsner S, Nickerson M (1968) A method for the study of mechanisms of drug disposition in smooth muscle. Can J Physiol Pharmacol 46:719–730

    Google Scholar 

  • Levin JA (1974) The uptake and metabolism of 3H-l- and 3H-dl-norepinephrine by intact rabbit aorta and by isolated adventitia and media. J Pharmacol Exp Ther 190:210–226

    Google Scholar 

  • Levin JA, Furchgott RF (1970) Interaction between potentiating agents of adrenergic amines in rabbit aortic strips. J Pharmacol Exp Ther 172:320–331

    Google Scholar 

  • Lindmar R, Muscholl E (1964) Die Wirkung von Pharmaka auf die Elimination von Noradrenalin aus der Perfusionsflüssigkeit und die Noradrenalinaufnahme in das isolierte Herz. Naunyn-Schmiedeberg's Arch Exp Pathol Pharmakol 247:469–492

    Google Scholar 

  • Maxwell RA, Eckhardt SB, Wastila WB (1968) Concerning the distribution of endogenous norepinephrine in the adventitial and media-intimal layers of the rabbit aorta and the capacity of these layers to bind tritiated norepinephrine. J Pharmacol Exp Ther 161:34–39

    Google Scholar 

  • Patil PN, Trendelenburg U (1982) The neuronal uptake and metabolism of 3H-noradrenaline in the rabbit iris. Naunyn-Schmiedeberg's Arch Pharmacol 318:158–165

    Google Scholar 

  • Starke K, Steppeler A, Zumstein A, Henseling M, Trendelenburg U (1980) False labelling of comercially available 3H-catecholamines? Naunyn-Schmiedeberg's Arch Pharmacol 311:109–112

    Google Scholar 

  • Török J, Bevan JA (1971) Entry of 3H-norepinephrine into the arterial wall. J Pharmacol Exp Ther 177:613–620

    Google Scholar 

  • Wyse DG (1974) On the role of neuronal uptake (uptake1) in the inactivation of noradrenaline by aortic strips. Can J Physiol Pharmacol 52:1102–1109

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the Deutsche Forschungsgemeinschaft (He 813)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henseling, M. The role of neuronal and extraneuronal uptake in the inactivation of 3H-(−)noradrenaline in the rabbit aorta determined by a method relating uptake with amine diffusion in the tissue. Naunyn-Schmiedeberg's Arch. Pharmacol. 324, 163–168 (1983). https://doi.org/10.1007/BF00503889

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00503889

Key words

Navigation