Prostaglandin E receptor EP3 subtype induces neurite retraction via small GTPase Rho.
Prostaglandin E receptor EP3 subtype is widely distributed in the nervous system and is specifically localized to neurons, suggesting that the EP3 receptor plays important roles in the nervous system. We established a PC12 cell line that stably expresses the EP3B receptor isoform isolated from bovine adrenal chromaffin cells and examined the effect of agonist stimulation on the neuronal morphology of the PC12 cells. In the differentiated cells, M&B28767, an EP3 agonist, caused neurite retraction in a pertussis toxin-insensitive manner. 12-O-Tetradecanoylphorbol-13-acetate (TPA) also induced neurite retraction. However, when protein kinase C was down-regulated by long term exposure to TPA, TPA failed to induce neurite retraction, while the EP3B receptor-mediated retraction occurred normally. Clostridium botulinum C3 exoenzyme completely inhibited both EP3 agonist- and TPA-induced neurite retraction when microinjected into the cells, indicating that the morphological effect of the EP3B receptor is dependent on Rho activity. Thus, the activation of the EP3B receptor induced neurite retraction through a protein kinase C-independent Rho-activation pathway.
Katoh
H
H
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606, Japan.
Negishi
M
M
Ichikawa
A
A
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001905:Botulinum Toxins; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D016501:Neurites; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016716:PC12 Cells; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011459:Prostaglandins E, Synthetic; D018078:Receptors, Prostaglandin E; C032405:11-deoxy-16-phenoxy-17,18,19,20-tetranorprostaglandin E1; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020558:GTP Phosphohydrolases; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate