Cytoskeletal regulation of the signal transduction of prostaglandin EP4 receptor. 1998

N Nishigaki, and C Chang, and A Ichikawa, and M Negishi
Department of Molecular Neurobiology, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606, Japan.

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.

UI MeSH Term Description Entries
D008870 Microtubules Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS. Microtubule
D003078 Colchicine A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE). Colchicine, (+-)-Isomer,Colchicine, (R)-Isomer
D003599 Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. Cytoplasmic Filaments,Cytoskeletal Filaments,Microtrabecular Lattice,Cytoplasmic Filament,Cytoskeletal Filament,Cytoskeletons,Filament, Cytoplasmic,Filament, Cytoskeletal,Filaments, Cytoplasmic,Filaments, Cytoskeletal,Lattice, Microtrabecular,Lattices, Microtrabecular,Microtrabecular Lattices
D003703 Demecolcine An alkaloid isolated from Colchicum autumnale L. and used as an antineoplastic. Colcemid,Colcemide,Colchamine,Demecolcine, (+-)-Isomer
D005576 Colforsin Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000262 Adenylyl Cyclases Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP. Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012969 Sodium Fluoride A source of inorganic fluoride which is used topically to prevent dental caries. Fluoristat,Ossin,Zymafluor,Fluoride, Sodium,Fluorides, Sodium,Fluoristats,Ossins,Sodium Fluorides,Zymafluors

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