Referenced in: none

Automatically associated channels: Kv10.1 , Slo1

Title: Regulation of type 1 IP₃ receptor expression by dopamine D2-like receptors via AP-1 and NFATc4 activation.

Authors: K Mizuno, K Kurokawa, S Ohkuma

Journal, date & volume: Neuropharmacology, 2013 Aug , 71, 264-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23597509

Abstract
Type 1 inositol 1,4,5-trisphosphate receptors (IP₃Rs-1), together with ryanodine receptors, are major calcium channels to regulate intracellular Ca²⁺ concentration. Although our recent report demonstrates the essential involvement of IP₃R-1 up-regulation induced by dopamine D1-like and D2-like receptor (D1 and D2R) stimulation in psychological dependence, exact regulatory mechanisms of IP₃R-1 expression by D2Rs have not yet been clarified. Mouse cerebral cortical neurons were treated with inhibitor of Ca²⁺-related signal transduction pathways coupling to D2Rs and used to analyze the mechanisms of IP₃R-1 expression regulated by transcriptional factor. A selective D2R agonist, quinpirole, up-regulated IP₃R-1 protein following its mRNA increase, which was significantly inhibited by gallein (a Gβγ modulator), U73122 (a phospholipase C inhibitor), BAPTA-AM (an intracellular calcium chelating reagent), W7 (a calmodulin inhibitor), KN-93 (a calmodulin-dependent protein kinases inhibitor), and FK506 (a calcineurin inhibitor). Immunocytochemical assessment showed that quinpirole increased expression of both cFos and phosphorylated-cJun in nucleus and enhanced translocation of NFATc4 complex to nucleus from cytoplasm. In addition, quinpirole directly recruited bindings between AP-1 and IP₃R-1 promoter region and between NFATc4 and IP₃R-1 promoter region. These results indicate that D2Rs enhance IP₃R-1 gene transcription via increased bindings of AP-1 and NFATc4 to IP₃R-1 promoter region after Gβγ activation.