title: Activation of CRHR2 exerts an inhibitory effect on the expression of collapsin response mediator protein 3 in hippocampal neurons.
abstract: Corticotropin-releasing hormone (CRH) family peptides as well as their receptors have been shown to exhibit various functions in hippocampus. However, effects of CRH receptors activation on collapsin response mediator protein 3 (CRMP3), the key protein for dendrite outgrowth and cell apoptosis, remain unclear. In the present study, we determined the effects of CRHR1 and CRHR2 on CRMP3 expression in cultured hippocampal neurons. CRH and urocortin II (UCNII) dose-dependently suppressed CRMP3 mRNA and protein expression. The inhibitory effect on CRMP3 expression was completely reversed by CRHR2 antagonist but not by CRHR1 antagonist. Investigations on the signaling pathways of UCNII showed that CRHR2 mediated UCNII-induced increase in phosphorylated phospholipase C (PLC)-β3 expression. Blocking PLC activity with U73122 and PKC with Gö6976 completely prevented UCNII-inhibited CRMP3 expression. Our results suggest that CRHR2 activation decrease CRMP3 expression in hippocampal neurons via a mechanism that is dependent on PLC/PKC signaling pathways.
authors.affiliation: Department of Physiology and The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Sheng
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Xu
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism; D054832:Urocortins / Q000378:metabolism
chemical_list: C101531:CRF receptor type 2; C485779:Dpysl4 protein, rat; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D010738:Type C Phospholipases