PT  - JOURNAL ARTICLE
AU  - Amy K. Jassen
AU  - Hong Yang
AU  - Gregory M. Miller
AU  - Elizabeth Calder
AU  - Bertha K. Madras
TI  - Receptor Regulation of Gene Expression of Axon Guidance Molecules: Implications for Adaptation
AID  - 10.1124/mol.105.021998
DP  - 2006 Jul 01
TA  - Molecular Pharmacology
PG  - 71--77
VI  - 70
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/70/1/71.short
4100  - http://molpharm.aspetjournals.org/content/70/1/71.full
SO  - Mol Pharmacol2006 Jul 01; 70
AB  - Axon guidance molecules, critical for neurodevelopment, are also implicated in morphological and other neurodaptative changes mediated by physiological or pharmacological events in adult brain. As an example, the psychostimulant cocaine markedly alters axon guidance molecules in adult brain of cocaine-treated rats. To decipher a potential link between drug-induced activation of G-protein-coupled receptors (GPCRs) and modulation of axon guidance molecules, we investigated whether GPCR activity in a SK-N-MC human neuroepithelioma cell line (which expresses low levels of D1 dopamine receptors) affects gene expression of axon guidance molecules (semaphorins, ephrins, netrins, and their receptors). Using real-time polymerase chain reaction, we identified 17 of 26 axon guidance molecules in these cells, with varying levels of expression. Forskolin, which raised intracellular cAMP levels 340%, increased EphA5, EphB2, and Neuropilin1 expression, paralleling reported changes in the rat hippocampus after cocaine treatment. The dopamine receptor agonist dihydrexidine, which raised cAMP levels 22%, promoted regulatory changes in EphrinA1, EphrinA5, EphB1, DCC, and Semaphorin3C, whereas (±)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF81297) altered EphA5, EphrinA1, EphrinA5, and neuropilin1. cAMP and other signal transduction pathways may regulate gene expression of axon guidance molecules, potentially linking monoamine receptor activation to signal transduction cascades, transcriptional regulation of axon guidance molecules, and alterations in neural networks.