title: The neurotrophic effects of PACAP in PC12 cells: control by multiple transduction pathways.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are closely related members of the secretin superfamily of neuropeptides expressed in both the brain and peripheral nervous system, and they exhibit neurotrophic and neurodevelopmental effects in vivo. Like the index member of the Trk receptor ligand family, nerve growth factor (NGF), PACAP promotes the differentiation of PC12 cells, a well-established cell culture model, to investigate neuronal differentiation, survival and function. Stimulation of catecholamine secretion and enhanced neuropeptide biosynthesis are effects exerted by PACAP at the adrenomedullary synapse in vivo and on PC12 cells in vitro through stimulation of the specific PAC1 receptor. Induction of neuritogenesis, growth arrest, and promotion of cell survival are effects of PACAP that occur in developing cerebellar, hippocampal and cortical neurons, as well as in the more tractable PC12 cell model. Study of the mechanisms through which PACAP exerts its various effects on cell growth, morphology, gene expression and survival, i.e. its actions as a neurotrophin, in PC12 cells is the subject of this review. The study of neurotrophic signalling by PACAP in PC12 cells reveals that multiple independent pathways are coordinated in the PACAP response, some activated by classical and some by novel or combinatorial signalling mechanisms.
authors.affiliation: Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research, University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Ravni
authors.forename: Steve
authors.initials: S
authors.lastname: Bourgault
authors.forename: Alexis
authors.initials: A
authors.lastname: Lebon
authors.forename: Philippe
authors.initials: P
authors.lastname: Chan
authors.forename: Ludovic
authors.initials: L
authors.lastname: Galas
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Bruno
authors.initials: B
authors.lastname: Gonzalez
authors.forename: Lee E
authors.initials: LE
authors.lastname: Eiden
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
mesh_terms: D000818:Animals; D009414:Nerve Growth Factors; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D009414:Nerve Growth Factors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide