Summary
The fate of isoprenaline (ISO) was studied in the intact rabbit aorta, as well as in the isolated adventitia and isolated media, by means of liquid scintillation counting of 3H-ISO and 3H-O-methylisoprenaline (OMI) as well as by autoradiography of tissues incubated with 2μM ISO. The 3 preparations accumulated and O-methylated ISO; O-methylation was proportionally higher in the intact vessel than in its constituents. The isolated adventitia differed from the other preparations in reaching a steady-state of cortexone-resistant accumulation after 8 min of incubation and in exhibiting an O-methylating capacity which was partly resistant to the COMT inhibitor, U-0521. The effect of cocaine gave evidence for a participation of neuronal uptake in the accumulation of the amine in the intact aorta. In the media, most of the accumulation occurred in smooth muscle cells and was reduced by cortexone and increased by U-0521; elastin and collagen, present both in the media and the adventitia, showed accumulation which was not affected by the inhibitory drugs studied.
The results show that in the rabbit aorta there is a corticosteroid-resistant uptake mechanism (which predominates in the adventitia) which involves structures devoid of COMT activity. Furthermore, smooth muscle cells represent, in the media, the extraneuronal metabolizing site of loss. The adventitia is a complex layer, with different types of cells which may intervene in accumulation and metabolism of ISO. Therefore, it is concluded that the isolated media represents an acceptable model for the study of both corticosteroidsensitive and-resistant extraneuronal mechanisms, whereas the isolated adventitia is characterized by the presence of neuronal and extraneuronal mechanisms.
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References
Azevedo I, Osswald W (1974) Uptake, distribution and metabolism of isoprenaline in the dog saphenous vein. Naunyn-Schmiedeberg's Arch Pharmacol 295:141–147
Bönisch H, Trendelenburg U (1974) Extraneuronal removal, accumulation and O-methylation of isoprenaline in the perfused heart. Naunyn-Schmiedeberg's Arch Pharmacol 283:191–218
Branco D, Osswald W (1980) The fate of isoprenaline after inhibition of O-methylation and of extraneuronal uptake. Eur J Pharmacol 67:247–253
Bryan LJ, O'Donnel SR (1979) Comparison of the effects of tropolone, B-thujaplicin and U-0521 on the extraneuronal accumulation of isoprenaline in guinea-pig trachealis smooth muscle cells. A quantitative fluorescence histochemical study. Naunyn-Schmiedeberg's Arch Pharmacol 307:235–241
Euler US von, Lishajko F (1961) Improved technique for the fluorimetric estimation of catecholamine. Acta Physiol Scand 51:348–355
Furchgott R, Bhadrakom S (1953) Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. J Pharmacol Exp Ther 108:129–143
Gillespie JS (1976) Extraneuronal uptake of catecholamines in smooth muscle and connective tissue. In: Paton D (ed) The mechanism of neuronal and extraneuronal transport of catecholamines. Raven Press, New York, pp 325–354
Graefe K-H, Bönisch H, Fiebig R, Trendelenburg U (1975) Extraneuronal uptake and metabolism of catecholamines in isolated perfused hearts. Proc Sixth Int Congress Pharmacol, vol 2. Helsinki, pp 117–130
Head RJ, de la Lande IS, Irvine RJ, Johnson SM (1980) Uptake and O-methylation of isoprenaline in the rabbit ear artery. Blood Vessels 17:229–245
Henseling M (1978) Contribution of neuronal and extraneuronal mechanisms to the elimination of noradrenaline from the extracellular space (rabbit aorta). Naunyn-Schmiedeberg's Arch Pharmacol 302:R50
Henseling M (1980) Distribution and metabolic fate of 3H-noradrenaline in rabbit aorta and their influence on muscle contraction. In: Bevan JA, Godfraind T, Maxwell RA, Vanhoutte PM (eds) Vascular neuroeffector mechanisms Raven Press, New York, pp 160–170
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
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
Henseling M, Rechtsteiner D, Trendelenburg U (1978) The influence of monoamine oxidase and catechol-O-methyltransferase on the distribution of 3H-(±)-noradrenaline in rabbit aortic strips. Naunyn-Schmiedeberg's Arch Pharmacol 302:181–194
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
Levin JA, Wilson SE (1977) The effect of monoamine oxidase and catechol O-methyltransferase inhibitors on the accumulation and metabolism of [l-3H]norepinephrine by the adventitia and media of rabbit aorta. J Pharmacol Exp Ther 203:598–609
Maxwell RA, Eckhardt SB, Wastila WB (1968) Concerning the distribution of endogenous norepinephrine in the adventitial and mediaintimal layers of the rabbit aorta and the capacity of these layers to bind tritiated norepinephrine. J Pharmacol Exp Ther 161:34–39
Osswald W, Garrett J, Guimarães S (1975) Extraneuronal uptake and metabolism in dog vascular structures. Proc Sixth Int Congress Pharmacol, vol 2. Helsinki, pp 149–158
Paiva MQ, Guimarães S (1978) A comparative study of the uptake and metabolism of noradrenaline and adrenaline by the isolated saphenous vein of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 303:221–228
Trendelenburg U (1980) A kinetic analysis of the extraneuronal uptake and metabolism of catecholamines. Rev Physiol Biochem Pharmacol 87:33–115
Weibel ER (1972) A stereological method for estimating volume and surface of sarcoplasmic reticulum. J Microsc (Oxf) 95:229–242
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Some of the results were presented to the 3rd Meeting on Adrenergic Mechanisms, Porto, July 12–13, 1978 (Proceedings, p. 93) and to the 1st Joint Meeting of the Spanish and Portuguese Pharmacological Societies (Santiago de Compostela, 21–23.5.79). Supported by Instituto Nacional de Investigação Científica (Centro de Farmacologia e Biopatologia Quimica-FmPl)
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Branco, D., Azevedo, I., Sarmento, A. et al. The fate of isoprenaline in the isolated rabbit aorta. Naunyn-Schmiedeberg's Arch. Pharmacol. 316, 120–125 (1981). https://doi.org/10.1007/BF00505304
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DOI: https://doi.org/10.1007/BF00505304