Summary
In the rat vas deferens (preloaded with 3H-noradrenaline, catechol-O-methyl transferase inhibited, calcium-free solution) ouabain, glucose deprivation or the combination of hypoxia plus presence of lactate were found to induce a carrier-mediated (desipramine-sensitive) outward transport of the 3H-amine. Glucose deprivation additionally increased the efflux of deaminated 3H-metabolites, as a consequence of an increased net leakage of vesicular 3H-noradrenaline; moreover, 3H-dihydroxymandelic acid then became the predominant neuronal metabolite. The simultaneous lack of oxygen and glucose resulted in a very pronounced release of the 3H-amine. Moreover, during spontaneous efflux more outward transport of 3H-noradrenaline was observed in the absence than in the presence of extracellular calcium.
In rat atria (under the same experimental conditions) the contribution by carrier-mediated outward transport to the spontaneous efflux of tritium exceeded that in vasa deferentia. Moreover, the efflux of lactate (as an index of hypoxia of the tissue) exceeded that observed in vasa deferentia, under aerobic and anaerobic conditions.
It is proposed that the greater contribution by outward transport of 3H-noradrenaline to spontaneous efflux in atria than in vasa deferentia does not reflect any basic difference between the varicosities in two different organs. It is likely that the less heterogeneous distribution of the 3H-amine in atria than in vasa deferentia is responsible for storage of the exogenous amine in atrial varicosities that are subject to some hypoxia, to an increased extracellular lactate level and to perhaps a minor degree of glucose deficiency; these factors may well be responsible for the difference with regard to outward transport of 3H-noradrenaline during spontaneous efflux. Thus, in addition to the heterogeneity of the distribution of 3H-noradrenaline, an additional heterogeneity with regard to the energy supply must be expected for incubated organs.
Similar content being viewed by others
Abbreviations
- COMT:
-
catechol-O-methyl transferase
- DOMA:
-
dihydroxymandelic acid
- DOPEG:
-
dihydroxyphenylglycol
- FRL:
-
fractional rate of loss
- MAO:
-
monoamine oxidase
References
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
Burt JM (1982) Electrical and contractile consequences of Na+ or Ca2+ gradient reduction in cultured heart cells. J Mol Cell Cardiol 14:99 -110
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
Graefe K-H, Stefano FJE, Langer SZ (1973) Preferential metabolism of (−)-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1160
Hamberger B (1967) Reserpine-resistant uptake of catecholamines in isolated tissues of the rat. Acta Physiol Scand 71 [Suppl] 295:1–56
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
Hohl CM, Altschuld RA, Brierley GP (1983) Effects of calcium on the permeability of isolated adult rat heart cells to sodium. Arch Biochem Biophys 221:197–205
Ishida Y, Paul RJ (1990) Effects of hypoxia on high-energy phosphagen content, energy metabolism and isometric force in guinea-pig taenia caeci. J Physiol (Lond) 424:41–56
Jain SK (1989) Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J Biol Chem 264:21340–21345
Paton DM (1968) Cation and metabolic requirements for retention of metaraminol by rat uterine horns. Br J Pharmacol 33:277–286
Paton DM (1972) Metabolic requirements for the uptake of noradrenaline by isolated atria and vas deferens of the rabbit. Pharmacol 7:78–88
Paton DM (1973) Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria. Br J Pharmacol 49:614–627
Pfleiderer G, Dose K (1955) Eine enzymatische Bestimmung der L[±]-Milchsäure mit Milchsäuredehydrogenase. Biochem Z 326:436–441
Powell T, Terrar DA, Twist VW (1980) Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol (Lond) 302:131–153
Schömig A, Fischer S, Kurz T, Richardt G, Scöbmig E (1987) Nonexocytotic release of endogenous noradrenaline in the ischemic and anoxic rat heart: mechanism and metabolic requirements. Circ Res 60:194–205
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
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
Schömig E, Schönfeld C-L, Halbrügge T, Graefe K-H, Trendelenburg U (1990) The heterogeneity of the neuronal distribution of exogenous noradrenaline in the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 342:160–170
Schrör K, Sadat-Khonsari A, Krebs R (1979) Different intracellular cation-content in right and left ventricle dependent on varying extracellular Ca2+-concentration. J Mol Cell Cardiol 11:45–55
Snedecor GW, Cochran GW (1980) Statistical methods. Iowa State University Press, Ames, Iowa, USA
Starke K (1978) Introduction. Proceedings of 3. Meeting on Adrenergic Mechanisms, Porto, pp 61–66
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
Sweadner KJ (1985) Ouabain-evoked norepinephrine release from intact rat sympathetic neurons: evidence for carrier-mediated release. J Neurosci 5:2397–2406
Trendelenburg U, Bönisch H, Graefe K-H, Henseling M (1979) The rate constants for the efflux of metabolites of catecholamines and phenethylamines. Pharmacol Rev 31:179–203
Wakade AR, Furchgott RF (1968) Metabolic requirements for the uptake and storage of norepinephrine by the isolated left atrium of the guinea pig. J Pharmacol Exp Ther 163:123–135
Author information
Authors and Affiliations
Additional information
Supported by the Dr. Robert Pfleger-Stiftung and the Deutsche Forschungsgemeinschaft (SFB 176)
Send offprint requests to H. Russ at the above address
Rights and permissions
About this article
Cite this article
Russ, H., Schömig, E. & Trendelenburg, U. The energy requirements for the basal efflux of 3H-noradrenaline from sympathetically innervated organs. Naunyn-Schmiedeberg's Arch Pharmacol 344, 286–296 (1991). https://doi.org/10.1007/BF00183002
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00183002