Summary
After pretreatment of rats with reserpine and pargyline (to inhibit vesicular uptake and monoamine oxidase, respectively) and after inhibition of catechol-O-methyl transferase (by U-0521) and in calcium-free solution, the adrenergic neurones of isolated vasa deferentia and atria were loaded with 3H-noradrenaline. The spontaneous efflux of 3H-noradrenaline and 3H-dihydroxyphenylglycol was determined, as well as the steady-state effect of two concentrations of desipramine.
On the basis of a mathematical model of the adrenergic nerve ending, fractional rates (FR = rate of flux divided by tissue tritium content) were calculated for unidirectional outward diffusion, for outward transport and for neuronal re-uptake (all for 3H-noradrenaline). Although the density of adrenergic innervation is lower in atria than in vasa deferentia, neuronal re-uptake amounted to about 90% of the spontaneous efflux of 3H-noradrenaline in both tissues.
While the FR for unidirectional outward diffusion was virtually the same in both tissues, the FR for outward transport of 3H-noradrenaline was more than three times higher in atria than in vasa deferentia. There is, as yet, no explanation for this pronounced difference.
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Abbreviations
- COMT:
-
catechol-O-methyl transferase
- DOMA:
-
dihydroxymandelic acid
- DOPEG:
-
dihydroxyphenylglycol
- FR:
-
fractional rate (= rate of flux divided by simultaneously determined tritium content of tissue)
- FRL:
-
fractional rate of loss (= rate of net efflux divided by simultaneously determined tritium content of tissue)
- MAO:
-
monoamine oxidase
References
Bönisch H (1984) The transport of (+)-amphetamine by the neuronal noradrenaline carrier. Naunyn-Schmiedeberg's Arch Pharmacol 327:267–272
Cassis L, Ludwig J, Grohmann M, Trendelenburg U (1986) The effect of partial inhibition of monoamine oxidase on the steady-state rate of deamination of 3H-catecholamines in two metabolizing systems. Naunyn-Schmiedeberg's Arch Pharmacol 333:253 - 261
Dubocovich M, Langer SZ (1973) Effects of flow-stop on the metabolism of noradrenaline released by nerve stimulation in the perfused spleen. Naunyn-Schmiedeberg's Arch Pharmacol 278:179–194
Fischer P, Burger A, Graefe K-H, Trendelenburg U (1989) The effect of (±)-dobutamine on adrenergic nerve endings. NaunynSchmiedeberg's Arch Pharmacol 339:79–84
Graefe K-H, Fuchs G (1979) On the mechanism of neuronal efflux of axoplasmic 3H-(−)-noradrenaline. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: Basic and clinical frontiers, vol 1. Pergamon Press, New York Oxford, pp 268–270
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
Grohmann M, Trendelenburg U (1984) The substrate specificity of uptake2 in the rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 328:164–173
Haefely W, Hürlimann A, Thoenen H (1964) A quantitative study of the effect of cocaine on the response of the cat nictitating membrane to nerve stimulation and to injected noradrenaline. Br J Pharmacol 22:5–21
Hermann W, Graefe K-H (1977) Relationship between the uptake of 3H-metaraminol and the density of adrenergic innervation in isolated rat tissues. Naunyn-Schmiedeberg's Arch Pharmacol 296:99–110
Hertting G (1965) Effect of drugs and sympathetic denervation on noradrenaline uptake and binding in animal tissues. In: Pharmacology of cholinergic and adrenergic transmission. Proceedings of the 2nd International Pharmacological Meeting, Prague. Pergamon Press, Oxford London New York, pp 277–289
Hertting G, Schiefthaler Th (1963) Beziehung zwischen Durchfluß-größe und Noradrenalinfreisetzung bei Nervenreizung der isoliert durchströmten Katzenmilz. Naunyn-Schmiedebergs Arch Exp Path Pharmacol 246: 13–14
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
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 336:602–610
Ludwig J, Halbrügge T, Vey G, Walter J, Graefe K-H (1989) Haemodynamics as a determinant of the pharmacokinetics of, and the plasma catecholamine responses to, isoprenaline. Fur J Clin Pharmacol (in press)
Moura D (1988) Libertagao, por diferentes estimulos, do noradrenalina endògena e de aminas exògenas incorporadas pelo terminal simpatico. Dr. Thesis, Medical Faculty, University of Porto, O'Porto, Portugal
Muscholl E (1959) Die Konzentration von Noradrenalin und Adrenalin in den einzelnen Abschnitten des Herzens. Naunyn-Schmiedeberg's Arch Pharmacol 237:350–364
Sammet S, Graefe K-H (1979) Kinetic analysis of the interaction between noradrenaline and Na+ in neuronal uptake: kinetic evidence of co-transport. Naunyn-Schmiedeberg's Arch Pharmacol 309:99–107
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
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. NaunynSchmiedeberg's Arch Pharmacol 339:433–440
Singer EA (1988) Transmitter release from brain slices elicited by single pulses: a powerful method to study presynaptic mechanisms. Trends Pharmacol Sci 9:274–276
Snedecor GW, Cochran WG (1980) Statistical methods, 7th edn. Iowa State University Press, Ames, Iowa, USA
Starke K (1987) Presynaptic a-autoreceptors. Rev Physiol Biochem Pharmacol 107:73–146
Starke K, Werner U, Hellerforth R, Schümann HJ (1970) Influence of peptides on the output of noradrenaline from isolated rabbit hearts. Eur J Pharmacol 9:136–140
Stefano FJE, Trendelenburg U (1984) Saturation of monoamine oxidase by intraneuronal noradrenaline accumulation. Naunyn-Schmiedeberg's Arch Pharmacol 328:135–141
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
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Schömig, E., Fischer, P., Schönfeld, C.L. et al. 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 (1989). https://doi.org/10.1007/BF00260604
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DOI: https://doi.org/10.1007/BF00260604