Modulation of intracellular calcium transients and dopamine release by neuropeptide Y in PC-12 cells.
In PC-12 cells differentiated with nerve growth factor, neuropeptide Y (NPY) potentiated the K(+)-evoked increase in intracellular calcium, but this potentiation was not mediated by classical Y1 or Y2 NPY receptors. The potentiation by NPY appeared to occur through the mobilization of calcium from intracellular stores because thapsigargin successfully blocked the potentiation. In contrast, the Y2 agonist, NPY-(13-36), attenuated the K(+)-evoked increase in intracellular calcium by decreasing the influx of extracellular calcium. The effect of NPY-(13-36) on dopamine release from PC-12 cells was next studied. NPY-(13-36) significantly attenuated the K(+)-evoked dopamine release in a concentration-dependent manner. Nifedipine and omega-conotoxin also attenuated the evoked dopamine release. In the presence of nifedipine or omega-conotoxin, NPY-(13-36) produced further inhibition of the evoked dopamine release. Furthermore, NPY-(13-36)-induced inhibition of dopamine release was abolished by pertussis toxin pretreatment. We conclude that the regulatory effects of NPY and analogues on intracellular calcium are mediated by multiple NPY receptor subtypes. Y2 receptor-mediated pertussis toxin-sensitive inhibition of the evoked dopamine release does not seem to be due to interactions with L- or N-type Ca2+ channels.
Chen
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Department of Pharmacological and Physiological Science, St. Louis University, Missouri 63104.
Westfall
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D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002454:Cell Differentiation; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D007425:Intracellular Membranes / Q000378:metabolism / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology*; D009994:Osmolar Concentration; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D010446:Peptide Fragments; C062924:neuropeptide Y (13-36); D011188:Potassium; D002118:Calcium; D004298:Dopamine