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)
Haass
M
M
Department of Cardiology, University of Heidelberg, Federal Republic of Germany.
Hock
M
M
Richardt
G
G
Schömig
A
A
D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D005089:Exocytosis / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000378:metabolism; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011863:Radioimmunoassay; D014439:Tyramine / Q000378:metabolism; D014701:Veratridine / Q000378:metabolism
D009478:Neuropeptide Y; D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-; D008734:Methoxyhydroxyphenylglycol; D014701:Veratridine; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D014439:Tyramine