Summary
The metabolism of 3H-noradrenaline released by nerve stimulation in the isolated nerve-muscle preparation of the cat nictitating membrane was determined under control conditions and in the presence of hydrocortisone, 28 μM, a concentration which inhibits the high affinity extraneuronal uptake of noradrenaline in this tissue. in the controls the main fraction in the overflow elicited by stimulation at 10 Hz during 2 min was the deaminated glycol, 3H-DOPEG (3,4-dihydroxyphenylglycol), which accounted for 45.2±2.96% of the total radioactivity. Under these conditions, 3H-noradrenaline represented 30.8±1.92%, while 3H-normetanephrine accounted for 14.5±0.94% of the total overflow of radioactivity. During exposure to hydrocortisone there was a selective inhibition in 3H-normetanephrine formation from 3H-noradrenaline released by stimulation while the other fractions were not affected significantly. In contrast to these results, there were no changes in the spontaneous outflow of 3H-normetanephrine during exposure to hydrocortisone. The results obtained support the view that 3H-normetanephrine in sponteneous release originates from the activity of prejunctional catechol-O-methyltransferase. On the other hand, 3H-normetanephrine formed during transmitter release elicited by nerve stimulation is due to the activity of extraneuronal catechol-O-methyltransferase. Access of 3H-noradrenaline released by nerve stimulation to extraneuronal catechol-O-methyltransferase is mediated through the high-affinity, hydrocortisone-sensitive extraneuronal uptake mechanism.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Cubeddu, L. X., Barnes, E. M., Langer, S. Z., Weiner, N.: Release of norepinephrine and dopamine-β-hydroxylase by nerve stimulation. I. Role of neuronal and extraneuronal uptake and of α-presynaptic receptors. J. Pharmacol. exp. Ther. 190, 431–450 (1974)
Dubocovich, M., Langer, S. Z.: 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 (1973)
Graefe, K. H., Stefano, F. J. E., Langer, S. Z.: Preferential metabolism of (-)-3H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem. Pharmacol. 22, 1147–1160 (1973)
Graefe, K. H., 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)
Iversen, L. L.: The uptake of catecholamine at high perfusion concentrations in the isolated rat heart: a novel catecholamine uptake process. Brit. J. Pharmacol. 25, 18–33 (1965)
Iversen, L. L., Langer, S. Z.: Effects of phenoxybenzamine on the uptake and metabolism of noradrenaline in the rat heart and vas deferens. Brit. J. Pharmacol. 37, 627–637 (1969)
Jarrott, B., Langer, S. Z.: Changes in monoamine oxidase and catechol-O-methyltransferase activities after denervation of the nicitating membrane of the cat. J. Physiol. (Lond.) 212 549–559 (1971)
Langer, S. Z.: The metabolism of 3H-noradrenaline released by electrical stimulation from the nictitating membrane of the cat and from the vas deferens of the rat. J. Physiol. (Lond.) 208, 515–546 (1970)
Langer, S. Z.: Selective metabolic pathways for noradrenaline in the peripheral and in the central nervous system. Med. Biol. 52, 372–383 (1974)
Langer, S. Z., Adler-Graschinsky, E., Almeida, A. P., Diniz, C. R.: Prejunctional effects of a purified toxin from the scorpion Tityus serrulatus release of 3H-noradrenaline and enhancement of transmitter overflow elicited by nerve stimulation. Naunyn-Schmiedeberg's Arch. Pharmacol. 287, 243–259 (1975)
Langer, S. Z., Enero, Ma. A.: The potentiation of responses to adrenergic nerve stimulation in the presence of cocaine: its relationship to the metabolic fate of released norepinephrine. J. Pharmacol. exp. Ther. 191, 431–443 (1974)
Langer, S. Z., Rubio, M. C.: Effects of the noradrenaline metabolites on the adrenergic receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 276, 71–88 (1973)
Langer, S. Z., Stefano, F. J. E., Enero, Ma. A.: Pre- and postsynaptic origin of the norepinephrine metabolites formed during transmitter release elicited by nerve stimulation. J. Pharmacol. exp. Ther. 183, 90–102 (1972)
Laverty, R., Taylor, K. M.: The flurometric assay of catecholamines and related compounds: Improvements and extensions to the hydroxyindole technique. Analyt. Biochem. 22, 269–279 (1968)
Snedecor, G. W., Cochran, W. G.: Statistical Methods, 6th. ed. Ames: The Iowa State University Press 1969
Tarlov, S., Langer, S. Z.: The fate of 3H-norepinephrine released from isolated atria and vas deferens: effect of field stimulation. J. Pharmacol. exp. Ther. 179, 186–197 (1971)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Luchelli-Fortis, M.A., Langer, S.Z. Selective inhibition by hydrocortisone of 3H-normetanephrine formation during 3H-transmitter release elicited by nerve stimulation in the isolated nerve-muscle preparation of the cat nictitating membrane. Naunyn-Schmiedeberg's Arch. Pharmacol. 287, 261–275 (1975). https://doi.org/10.1007/BF00501472
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00501472