Pituitary adenylate cyclase-activating polypeptide promotes differentiation of mouse neural stem cells into astrocytes.
We have found that pituitary adenylate cyclase-activating polypeptide (PACAP) employed at the physiological concentrations induces the differentiation of mouse neural stem cells into astrocytes. The differentiation process was not affected by cAMP analogues such as dibutylic cAMP (db-cAMP) or 8Br-cAMP or by the specific competitive inhibitor of protein kinase A, Rp-adenosine-3',5'-cyclic monophosphothioate triethylamine salt (Rp-cAMP). Expression of the PACAP receptor (PAC1) in neural stem cells was detected by both RT-PCR and immunoblot using an affinity-purified antibody. The PACAP selective antagonist, PACAP(6-38), had an inhibitory effect on the PACAP-induced differentiation of neural stem cells into astrocytes. These results indicate that PACAP acts on the PAC1 receptor on the plasma membrane of mouse neural stem cells, with the signal then transmitted intracellularly via a PAC1-coupled G protein, does not involve Gs. This signaling mechanism may thus play a crucial role in the differentiation of neural stem cells into astrocytes.
Ohno
Fusako
F
Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Watanabe
Jun
J
Sekihara
Hohkai
H
Hirabayashi
Takahiro
T
Arata
Satoru
S
Kikuyama
Sakae
S
Shioda
Seiji
S
Nakaya
Kazuyasu
K
Nakajo
Shigeo
S
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009417:Nerve Tissue / Q000166:cytology / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013234:Stem Cells / Q000502:physiology*
C495402:Adcyap1 protein, mouse; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide