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The Journal of Neuroscience, August 1, 2002, 22(15):6560-6569

Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Inhibit Dendritic Growth in Cultured Sympathetic Neurons

Karen Drahushuk¹, Terry D. Connell², and Dennis Higgins¹

Departments of ¹ Pharmacology and Toxicology and ² Microbiology and the Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, New York 14214

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 VPAC₂ receptors. 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.

Key words: vasoactive intestinal peptide; pituitary adenylate cyclase activating polypeptide; BMP-7; cAMP; dendrite; sympathetic

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22156560-10$05.00/0

This article has been cited by other articles:

				G.-X. Shi, L. Jin, and D. A. Andres Pituitary Adenylate Cyclase-Activating Polypeptide 38-Mediated Rin Activation Requires Src and Contributes to the Regulation of Hsp27 Signaling during Neuronal Differentiation Mol. Cell. Biol., August 15, 2008; 28(16): 4940 - 4951. [Abstract] [Full Text] [PDF]

				I.-J. Kim, K. M. Drahushuk, W.-Y. Kim, E. A. Gonsiorek, P. Lein, D. A. Andres, and D. Higgins Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons J. Neurosci., March 31, 2004; 24(13): 3304 - 3312. [Abstract] [Full Text] [PDF]

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