Elsevier

Neuroscience

Volume 28, Issue 2, 1989, Pages 475-486
Neuroscience

Co-release of neuropeptide Y and noradrenaline from pig spleen in vivo: Importance of subcellular storage, nerve impulse frequency and pattern, feedback regulation and resupply by axonal transport

https://doi.org/10.1016/0306-4522(89)90193-0Get rights and content

Abstract

The importance of subcellular storage, nerve impulse rate and pattern, and feedback regulation, as well as resupply by axonal transport for the release of noradrenaline and neuropeptide Y-like immunoreactivity, was studied in the blood perfused pig spleen in vivo. Vasoconstrictor responses were recorded as perfusion pressure changes. Subcellular fractionation experiments using sucrose density gradients showed a bimodal distribution of noradrenaline (peak concentrations at 0.8 and 1.1 M sucrose) while only one main peak of neuropeptide Y was present (at 1. l M sucrose). Overflow suggesting release of noradrenaline and neuropeptide Y-like immunoreactivity could be detected after 10s stimulation at 10 Hz. The ratio for the output of noradrenaline and neuropeptide Y upon continuous nerve stimulation in control animals decreased with frequency. After inhibition of noradrenaline reuptake by desipramine the vasoconstrictor response and noradrenaline output were enhanced while the corresponding overflow of neuropeptide Y was reduced by 50% at 0.5 Hz. Stimulation with the irregular or regular bursting patterns at high frequencies caused larger perfusion pressure increase and relative enhancement of neuropeptide Y output compared to noradrenaline than a continuous stimulation both before and after desipramine treatment. A similar fractional release per nerve impulse was calculated both for [3H]noradrenaline (5.6± 1.0 × 10−5) and neuropeptide Y (7.3±0.3 × 10−5). After reserpine treatment combined with preganglionic denervation the vasoconstrictor responses were more long-lasting, neuropeptide Y release was enhanced while noradrenaline content and release were reduced by 99%. The difference in neuropeptide Y overflow between continuous and bursting types of stimulation was smaller after reserpine treatment. After prolonged intermittent stimulation with regular bursts (20 Hz) for l h the splenic content of neuropeptide Y was reduced by 58%, while no change was observed for noradrenaline. The maximal perfusion pressure increase upon prolonged nerve stimulation after reserpine was similar in control and reserpine-treated animals, but after reserpine the vasoconstrictor response and neuropeptide Y release were subjected to fatigue. Ligation experiments of the splenic nerves revealed the splenic neuropeptide Y content was resupplied by axonal transport with a calculated total tissue turnover time of 11 days. In contrast, axonal transport contributed only to a marginal extent for the resupply of noradrenaline.

In conclusion, stimulation with high frequency bursting preferentially enhanced overflow of neuropeptide Y compared to the co-existing classical transmitter noradrenaline, suggesting that exocytosis of material from large dense-cored vesicles mainly occurred under such stimulation conditions. The local biophase concentrations of noradrenaline seem to regulate neuropeptide Y release. Due to the limited resupply by axonal transport, excessive and prolonged release of neuropeptide Y cannot be maintained without depletion of terminal stores.

Reference (45)

  • BiniG. et al.

    Thermoregulatory and rhythm generating mechanisms governing the sudomotor and vasoconstrictor outflow in human cutaneous nerves

    J. Physiol., Lond.

    (1980)
  • BrimijoinS.

    Transport and turnover of dopamine-beta-hydroxylase (EC 1.14.2.1) in sympathetic nerves of the rat

    J. Neurochem.

    (1972)
  • ChubbJ.W. et al.

    Evidence for two types of noradrenaline storage particles in dog spleen

    Nature

    (1970)
  • CubedduL.X. et al.

    Release of norepinephrine and dopamine-betahydroxylase by nerve Stimulation. I. Role of neuronal and extraneuronal uptake and of alpha-presynaptic receptors

    J. Pharmac. exp. Ther.

    (1974)
  • DeliusW. et al.

    General characteristics of sympathetic activity in human muscle nerves

    Acta physiol. scand.

    (1972)
  • Eckberg D. L., Rea R., Andersson O., Hedner T., Pernow J., Lundberg J. M. and Wallin B. G. Baroreflex modulation of...
  • EslerM.

    Assessment of sympathetic nerves function in humans from noradrenaline plasma kinetics

    Clin. Sci.

    (1982)
  • FriedG.

    Small noradrenergic storage vesicles isolated from rat vas deferens—biochemical and morphological characterization

    Acta physiol. scand. Suppl.

    (1980)
  • FriedG. et al.

    Subcellular storage and axonal transport of neuropeptide Y (NPY) in relation to catecholamines in the cat

    Acta physiol. scand.

    (1985)
  • FriedG. et al.

    Evidence for differential localization of noradrenaline and neuropeptide Y (NPY) in neuronal storage vesicles isolated from rat vas deferens

    J. Neurosci.

    (1985)
  • FriedG. et al.

    Neuropeptide Y, enkephalin and noradrenaline coexist in sympathetic neurons innervating the bovine spleen

    Cell Tiss. Res.

    (1986)
  • GeffenL.B. et al.

    Transport of noradrenaline in sympathetic nerves and the effect of nerve impulses on its contribution to transmitter stores

    J. Neurochem.

    (1968)
  • Cited by (0)

    View full text