PACAP action in nervous system development, regeneration, and neuroblastoma cell proliferation.
Pituitary adenylate cyclase activating peptide (PACAP) may play a role in neurogenesis, nerve injury, and neural tumor growth. A PACAP ligand receptor system functionally coupled to cAMP production was found to be expressed in the embryonic mouse neural tube at the onset of neurogenesis. PACAP was found to inhibit DNA synthesis and antagonize sonic hedgehog signaling in cells isolated from the neural tube, suggesting that PACAP interacts with patterning factors to regulate neurogenesis and phenotypic specification in the developing CNS. PACAP and PACAP receptor (PAC1) mRNA levels were strongly increased and decreased, respectively, in motor neurons in adult rats after facial nerve axotomy, indicating that PACAP may also act in nerve regeneration. Experiments using a neuroblastoma tumor cell line model indicate that PACAP may execute growth-related functions by activating MAP kinase in addition to cAMP-dependent protein kinase A.
Waschek
J A
JA
Department of Psychiatry, Mental Retardation Research Center, and Jonsson Cancer Center, University of California at Los Angeles, Los Angeles, California 90024, USA. jwaschek@mednet.ucla.edu
Dicicco-Bloom
E M
EM
Lelievre
V
V
Zhou
X
X
Hu
Z
Z
D000818:Animals; D019771:Axotomy; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D066298:In Vitro Techniques; D051379:Mice; D009046:Motor Neurons / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009420:Nervous System / Q000187:drug effects* / Q000196:embryology*; D009447:Neuroblastoma / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; C495504:Adcyap1r1 protein, mouse; C495505:Adcyap1r1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D004247:DNA