CYTOSKELETAL REGULATION OF THE SIGNAL-TRANSDUCTION OF PROSTAGLANDIN EP4 RECEPTOR

Prostaglandin (PG) EP4 receptor is coupled to Gs, stimulating adenylat e cyclase. We tested whether cytoskeleton modulates the signal transdu ction of the EP4 receptor. A microtubule depolymerizing agent, colcemi d, enhanced the PGE(2)-induced cAMP formation in the cloned EP4 recept or-expressing Chinese hamster ovary cells, but enhanced neither NaF pl us AlCl3 nor forskolin-induced cAMP formation. Other microtubule depol ymerizing agents, including colchicine, also induced the enhancement. These effects stemmed from the action of the agents on microtubules, b ecause beta-lumicolchicine, an inactive isomer of colchicine, had no e ffect. In contrast, the microfilament depolymerizing agents did not af fect the PGE(2)-induced cAMP formation but potentiated the enhancing e ffect of colcemid. This enhancement by colcemid was not due to the sup pression of the desensitization of the EP4 receptor. The enhancing eff ect of colcemid was also observed in another Gs-coupled PGE receptor s ubtype, EP2 receptor. These results demonstrate that the state of micr otubule assembly modulates the signal transduction of the EP4 receptor in concert with microfilament. (C) 1998 Published by Elsevier Science B.V.