Cytoskeletal regulation of the signal transduction of prostaglandin EP4 receptor.
Prostaglandin (PG) EP4 receptor is coupled to Gs, stimulating adenylate cyclase. We tested whether cytoskeleton modulates the signal transduction of the EP4 receptor. A microtubule depolymerizing agent, colcemid, enhanced the PGE2-induced cAMP formation in the cloned EP4 receptor-expressing Chinese hamster ovary cells, but enhanced neither NaF plus AlCl3 nor forskolin-induced cAMP formation. Other microtubule depolymerizing agents, including colchicine, also induced the enhancement. These effects stemmed from the action of the agents on microtubules, because beta-lumicolchicine, an inactive isomer of colchicine, had no effect. In contrast, the microfilament depolymerizing agents did not affect the PGE2-induced cAMP formation but potentiated the enhancing effect of colcemid. This enhancement by colcemid was not due to the suppression of the desensitization of the EP4 receptor. The enhancing effect of colcemid was also observed in another Gs-coupled PGE receptor subtype, EP2 receptor. These results demonstrate that the state of microtubule assembly modulates the signal transduction of the EP4 receptor in concert with microfilament.
Nishigaki
N
N
Department of Molecular Neurobiology, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606, Japan.
Chang
C
C
Ichikawa
A
A
Negishi
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D003078:Colchicine / Q000031:analogs & derivatives / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology*; D003703:Demecolcine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015398:Signal Transduction / Q000502:physiology*; D012969:Sodium Fluoride / Q000494:pharmacology
D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D005576:Colforsin; D012969:Sodium Fluoride; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D003078:Colchicine; D003703:Demecolcine