Pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide inhibit dendritic growth in cultured sympathetic neurons.
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 approximately 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.
Drahushuk
Karen
K
Department of Pharmacology and Toxicology and the Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, New York 14214, USA. drahushu@buffalo.edu
Connell
Terry D
TD
Higgins
Dennis
D
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; C495505:Adcyap1r1 protein, rat; D000067956:Adenylyl Cyclase Inhibitors; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D016212:Transforming Growth Factor beta; C495508:Vipr1 protein, rat; C495511:Vipr2 protein, rat; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP