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Neuropeptide Y differentiates between exocytotic and nonexocytotic noradrenaline release in guinea-pig heart

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Summary

The overflow of neuropeptide Y (NPY; radioimmunoassay), noradrenaline and dihydroxyphenylethylenglycol (DOPEG; high pressure liquid chromatography) from guinea-pig perfused hearts was investigated in relationship to exocytotic and nonexocytotic release mechanisms.

Exocytotic release: Electrical stimulation of the left stellate ganglion (12 Hz; 1 min) evoked a calcium-dependent overflow of noradrenaline and NPY, that was accompanied by a minor and prolonged increase in DOPEG overflow. This increase in DOPEG overflow was attenuated by blockade of neuronal amine re-uptake. In the presence of calcium, a closely related co-release of noradrenaline and NPY was also observed during administration of veratridine (10 μM); it was completely prevented by tetrodotoxin (1 μM). Nonexocytotic release: In the absence of extracellular calcium, veratridine (30 μM) induced noradrenaline overflow only when combined with the reserpine-like agent Ro 4-1284 (10 μM). This overflow was accompanied by efflux of DOPEG, but not of NPY. Similarily, tyramine (1–100 μM) induced a calcium-independent concomitant overflow of both noradrenaline and DOPEG, but not of NPY. During anoxic and glucose-free perfusion a predominantly calcium-independent overflow of noradrenaline was observed; only in the presence of extracellular calcium was this overflow accompanied by a minor overflow of NPY. Noradrenaline overflow, induced by veratridine plus Ro 4-1284 (in the absence of calcium), by tyramine, or by anoxia, was suppressed by blockade of neuronal amine re-uptake, and was, therefore, mediated by reversed transmembrane amine transport by the neuronal uptake1 carrier.

The results indicate that NPY is co-released with noradrenaline only during calcium-dependent exocytosis. On the other hand, whenever, noradrenaline is released by non-exocytotic (calcium-independent and carrier-mediated) release mechanisms, no substantial NPY overflow is observed. The simultaneous determination of noradrenaline and NPY overflow, therefore, allows a differentiation between exocytotic and nonexocytotic noradrenaline release, and NPY may be utilized as a marker of exocytotic noradrenaline release.

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Authors and Affiliations

  1. Department of Cardiology, University of Heidelberg, Bergheimer Straße 58, D-6900, Heidelberg, Germany

    Markus Haass, Michaela Hock, Gert Richardt & Albert Schömig

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  1. Markus Haass
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  2. Michaela Hock
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  3. Gert Richardt
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  4. Albert Schömig
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This work was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 320 — Herzfunktion und ihre Regulation)

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Haass, M., Hock, M., Richardt, G. et al. Neuropeptide Y differentiates between exocytotic and nonexocytotic noradrenaline release in guinea-pig heart. Naunyn-Schmiedeberg's Arch Pharmacol 340, 509–515 (1989). https://doi.org/10.1007/BF00260605

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