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

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 microM); it was completely prevented by tetrodotoxin (1 microM). Nonexocytotic release: In the absence of extracellular calcium, veratridine (30 microM) induced noradrenaline overflow only when combined with the reserpine-like agent Ro 4-1284 (10 microM). This overflow was accompanied by efflux of DOPEG, but not of NPY. Similarily, tyramine (1-100 microM) 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 uptake carrier. The results indicate that NPY is co-released with noradrenaline only during calcium-dependent exocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)