RT Journal Article
SR Electronic
T1 Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Inhibit Dendritic Growth in Cultured Sympathetic Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6560
OP 6569
DO 10.1523/JNEUROSCI.22-15-06560.2002
VO 22
IS 15
A1 Karen Drahushuk
A1 Terry D. Connell
A1 Dennis Higgins
YR 2002
UL http://www.jneurosci.org/content/22/15/6560.abstract
AB Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are related neuropeptides that are released by the preganglionic sympathetic axons. These peptides have previously been implicated in the regulation of sympathetic neurotransmitter metabolism and cell survival in postganglionic sympathetic neurons. In this study we consider the possibility that PACAP and VIP also affect the morphological development of these neurons. Postganglionic rat sympathetic neurons formed extensive dendritic arbors after exposure to bone morphogenetic protein-7 (BMP-7)in vitro. PACAP and VIP reduced BMP-7-induced dendritic growth by ∼70–90%, and this suppression was maintained for 3 weeks. However, neither PACAP nor VIP affected axonal growth or cell survival. The actions of PACAP and VIP appear to be mediated by PAC1 receptors because their effects were suppressed by an antagonist that binds to PAC1 and VPAC2 receptors (PACAP6–38), but not by an antagonist that binds to the VPAC1 and VPAC2receptors. Moreover, exposure to PACAP and VIP caused phosphorylation and nuclear translocation of cAMP response element-binding protein, and agents that increase the intracellular concentration of cAMP mimicked the PACAP-induced inhibition of dendritic growth. These data suggest that peptides released by preganglionic nerves modulate dendritic growth in sympathetic neurons by a cAMP-dependent mechanism.