Xl. Chen et al., AUTORECEPTOR-INDUCED INHIBITION OF NEUROPEPTIDE-Y RELEASE FROM PC-12 CELLS IS MEDIATED BY Y-2 RECEPTORS, American journal of physiology. Heart and circulatory physiology, 42(4), 1997, pp. 1737-1744
Pheochromocytoma (PC)-12 cells express Y-1, Y-2, and Y-3 neuropeptide
Y (NPY) receptors when differentiated with nerve growth factor (NGF).
The present work evaluated NGF-differentiated PC-12 cells as a model s
ystem to study modulation of NPY release by NPY autoreceptors. We demo
nstrated that both K+ and nicotine stimulated concomitant release of N
PY and dopamine from differentiated PC-12 cells. We also showed in thi
s study that NPY release from PC-12 cells was attenuated in a concentr
ation-dependent manner by peptide YY (PYY)-(13-36), a selective agonis
t for the Y-2 type of NPY receptors. This result demonstrated that NPY
release could be modulated by NPY autoreceptors of the Y-2 subtype. T
he inhibitory action of PYY-(13-36) may be mediated at least in part b
y inhibition of N-type Ca2+ channels, because PYY-(13-36) could not pr
oduce further inhibitory effects in the presence of a maximum effectiv
e concentration of omega-conotoxin, an N-type Ca2+-channel blocker. Th
e inhibition by PYY-(13-36) could be blocked by pretreatment of cells
with pertussis toxin, suggesting that an inhibitory GTP-binding protei
n was involved. Furthermore, the function of NPY autoreceptors could b
e modulated by other receptors such as beta-adrenergic and ATP recepto
rs. The evoked release of NPY was also attenuated by ATP and adenosine
, which have been shown to be colocalized and coreleased with NPY from
sympathetic nerve terminals. These results suggest that PC-12 cells d
ifferentiated with NGF may be an ideal model to study regulatory mecha
nisms of NPY release and that autoreceptor-mediated regulation of NPY
release appears to act through the Y-2 subtype of the NPY receptor.