Pituitary adenylate cyclase-activating polypeptide enhances Ca(2+)-dependent neurotransmitter release from PC12 cells and cultured cerebellar granule cells without affecting intracellular Ca(2+) mobilization.
The effects of pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide isolated from mammalian hypothalamus, was investigated on neurotransmitter release from clonal rat pheochromocytoma PC12 cells and cultured rat cerebellar granule cells. We found that PACAP38 stimulates the neurotransmitter release from PC12 cells by two distinct mechanisms in different concentration ranges. In the lower concentration range (<1 nM), PACAP38 enhanced depolarization- and ionomycin-dependent dopamine release without mobilizing intracellular Ca(2+), while in the higher concentration range (>1 nM), PACAP38 induced profound Ca(2+) influx and concomitant dopamine release from PC12 cells. In cultured rat cerebellar granule cells, PACAP38 failed to increase intracellular Ca(2+); however, it enhanced depolarization-dependent glutamate release remarkably. These results indicate that PACAP38 enhances Ca(2+)-dependent neurotransmitter release by modulating step(s) subsequent to Ca(2+) entry.
Aoyagi
K
K
Department of Life Sciences (Biology), University of Tokyo, Meguro-ku, Tokyo, 153-8902, Japan.
Takahashi
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003593:Cytoplasm / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018698:Glutamic Acid; D015759:Ionomycin; D002118:Calcium; D004298:Dopamine