Pituitary adenylate cyclase activating polypeptide regulates the basal production of nitric oxide in PC12 cells.
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), two members of the VIP/secretin/glucagon family, modulate neurotransmission via stimulation of protein kinases including cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in the central and peripheral nervous systems. They are reported to co-exist with nitric oxide synthases (NOSs) and other neuropeptides within the nervous system and peripheral tissues. In the present study, we investigated the neuronal role of these peptides in NO production in PC12 cells. We showed that PACAP decreased NO production in a dose-dependent manner, and the activators of protein kinase A and C also inhibited the NO production in PC12 cells. RT-PCR experiments demonstrated that PC12 cells constitutively express the mRNAs for neuronal NOS and the PACAP-specific (PAC1) receptor, and we concluded that PACAP plays an important role in the regulation of nNOS activity through PAC1 receptor in PC12 cells.
Onoue
Satomi
S
Health Science Division, Itoham Foods Inc., 1-2, Kubogaoka, Moriya, Ibaraki 302-0104, Japan. onoue@fureai.or.jp
Endo
Kosuke
K
Yajima
Takehiko
T
Kashimoto
Kazuhisa
K
D000704:Analysis of Variance; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; 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
C495403:Adcyap1 protein, rat; D008934:Mitogens; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D009569:Nitric Oxide; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase