Summary
The role played by extraneuronal sites in the disposition of noradrenaline and adrenaline was studied in the saphenous vein and in the mesenteric artery of the dog, taking as parameters the influence of blockade of these sites on the sensitivity to and on the time for half-relaxation (t 50) (both in oil and in Krebs solution) of these agonists. Preliminary experiments have shown that the t 50 values are not significantly changed by the changes in the height of the contraction provided the contraction is caused by the same concentration of the agonist.
The results obtained permit us to conclude that in both vessels the removal of amines depends on the concentrations used. In low (0.023 and 0.23 μM) or in moderately high (2.3 μM) concentrations, adrenaline is removed preferentially by extraneuronal sites, whereas noradrenaline “preferred” neuronal sites.
The selectivity of adrenaline for extraneuronal sites was present for such low concentrations that a possible physiological role of these sites in the inactivation of circulating adrenaline must be considered.
The results obtained by studying the relaxation in oil or in Krebs solution and by using cortexone (60 μM) or U-0521 (dihydroxy-2-methyl propiophenone; 0.1 mM) support the view that, at least in the vein, adrenaline may accumulate in extraneuronal cells and diffuse back into the biophase during the relaxation, thereby slowing the latter.
Both in the veins and in the arteries noradrenaline was inactivated more rapidly than adrenaline. The difference in the rate of inactivation of these amines, already observed in controls (when all inactivation pathways are operative) became more marked when both neuronal and extraneuronal sites were blocked. The existence of an important pathway not blocked by cocaine + cortexone + iproniazid which may preferentially inactivate noradrenaline cannot be ruled out.
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References
Avakian, O. V., Gillespie, J. S.: Uptake of noradrenaline by adrenergic nerves, smooth muscle and connective tissue in isolated perfused arteries and its correlation with the vasoconstrictor response. Brit. J. Pharmacol. Chemother. 32, 168–184 (1968)
Bönisch, H., Uhlig, W., Trendelenburg, U.: Analysis of the compartments involved in the extraneuronal storage and metabolism of isoprenaline in the perfused heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 283, 223–244 (1974)
Brandão, F., Guimarães, S.: Inactivation of endogenous noradrenaline released by electrical stimulation in vitro of dog saphenous vein. Blood Vessels 11, 45–54 (1974)
De la Lande, I. S., Harvey, J. A., Holt, S.: Responses of the rabbit coronary arteries to autonomic agents. Blood Vessels 11, 319–337 (1974)
Giles, R. E., Miller, J. W.: Studies on the potentiation of the inotropic actions of certain catecholamines by U-0521 (3′-4′-dihydroxy-α-methyl propiophenone). J. Pharmacol. exp. Ther. 157, 55–61 (1967)
Gillespie, J. S., Hamilton, D. N. H.: A possible active transport of noradrenaline into arterial smooth muscle cells. J. Physiol. (Lond.) 192, 30 P (1967)
Graefe, K., Trendelenburg, U.: 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 (1974)
Guimarães, S.: The slopes of cumulative and non-cumulative doseresponse curves for noradrenaline and isoprenaline. Europ. J. Pharmacol. 17, 44–49 (1972)
Guimarães, S.: Further study of the adrenoceptors of the saphenous vein of the dog: influence of factors which interfere with the concentrations of agonists at the receptor level. Europ. J. Pharmacol. 34, 9–19 (1975)
Guimarães, S., Osswald, W.: Adrenergic receptors in the veins of the dog. Europ. J. PHarmacol. 5, 133–140 (1969)
Guimarães, S., Osswald, W., Cardoso, W., Branco, D.: The effects of cocaine and denervation on the sensitivity to noradrenaline, its uptake and termination of its action in isolated venous tissue. Naunyn-Schmiedebergs Arch. Pharmak. 271, 262–273 (1971)
Guimarães, S., Azevedo, I., Cardoso, W., Oliveira, M. C.: Relation between the amount of smooth muscle of venous tissue and the degree of supersensitivity to isoprenaline caused by inhibition of catechol-O-methyl transferase. Naunyn-Schmiedeberg's Arch. Pharmacol. 286, 401–412 (1975)
Iversen, L. L.: The uptake of catechol amines at high perfusion concentrations in the rat isolated heart: a novel catechol amine uptake process. Brit. J. Pharmacol. Chemother. 25, 18–33 (1965)
Iversen, L. L., Salt, J.: Inhibition of catecholamine “uptake2” by steroids in the isolated rat heart. Brit. J. Pharmacol. Chemother. 40, 528–530 (1970)
Kalsner, S.: Role of extraneuronal mechanisms in the termination of contractile responses to amines in vascular tissue. Brit. J. Pharmacol. Chemother. 53, 267–277 (1975)
Kalsner, S., Nickerson, M.: A method for the study of mechanisms of drug disposition in smooth muscle. Canad. J. Physiol. Pharmacol. 46, 719–730 (1968)
Levin, J.: 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 (1974)
Lightman, S. L., Iversen, L. L.: The role of uptake2 in the extraneuronal metabolism of catecholamines in the isolated rat heart. Brit. J. Pharmacol. Chemother. 37, 638–649 (1969)
Muscholl, E.: Effect of cocaine and related drugs on the uptake of noradrenaline by heart and spleen. Brit. J. Pharmacol. Chemother. 16, 352–359 (1961)
Osswald, W., Branco, D.: The effects of drugs and denervation on removal and accumulation of nordrenaline in the perfused hind-limb of the dog. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, 175–190 (1973)
Osswald, W., Garrett, J., Guimarães, S.: Extraneuronal uptake and metabolism in dog vascular structures. Proceedings VIth Int. Cong. Pharmacol., Vol. 2, Helsinki 1975
Trendelenburg, U.: Redistribution of noradrenaline as a determinant of the rate of relaxation of rabbit aortic strips after incubation with noradrenaline. 5th International Congress on Pharmacology, Abstracts of Volunteer Papers, p. 235, San Francisco, Calif. (1972)
Trendelenburg, U., Henseling, M.: Factors determining the rate of relaxation of rabbit aortic strips after an exposure to noradrenaline. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 235–244 (1976)
Whitby, L. G., Hertting, G., Axelrod, J.: Effect of cocaine on the disposition of noradrenaline labelled with tritium. Nature (Lond.) 187, 604–605 (1960)
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This study was supported by a grant from the Instituto de Alta Cultura (PMC-2)
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Guimarães, S., Paiva, M.Q. The role played by the extraneuronal system in the disposition of noradrenaline and adrenaline in vessels. Naunyn-Schmiedeberg's Arch. Pharmacol. 296, 279–287 (1977). https://doi.org/10.1007/BF00498694
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DOI: https://doi.org/10.1007/BF00498694