Pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide attenuate glutamate-induced nNOS activation and cytotoxicity.
Both vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) act as neurotransmitters in the central and peripheral nervous systems. Attention has been focused on these neuropeptides because among their numerous biological activities, they have been confirmed to show neuroprotective effects against ischemia and glutamate-induced cytotoxicity. It is well established that glutamate has excitatory effects on neuronal cells, and that excessive glutamate shows potent neurotoxicity, especially in neuronal nitric oxide synthase-containing neurons. Glutamate stimulates the production of nitric oxide (NO) in neurons, and the NO generated is tightly associated with the delayed death of neurons. We examined the effects of these neuropeptides on the glutamate-induced neural actions using PC12 cells, and we confirmed the important activities of PACAP/VIP on the production of NO as well as the delayed cell death stimulated by glutamate.
Health Science Division, Itoham Foods Inc., Ibaraki 302-0104, Moriya, Japan.
Satomi
S
Onoue
Kosuke
K
Endo
Takehiko
T
Yajima
Kazuhisa
K
Kashimoto
D000818:Animals; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D009479:Neuropeptides / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000032:analysis; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018005:Receptors, Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000138:chemical synthesis / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D009573:Nitrites; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat