title: Effects of the prostanoids on the proliferation or hypertrophy of cultured murine aortic smooth muscle cells.
abstract: Effects of the prostanoids on the growth of cultured aortic vascular smooth muscle cells (VSMCs) were examined using mice lacking prostanoid receptors. Proliferation of VSMCs was assessed by measuring [(3)H]-thymidine incorporation and the cell number, and their hypertrophy by [(14)C]-leucine incorporation and protein content. In VSMCs from wild-type mice, expressions of mRNAs for the EP(4) and TP were most abundant, followed by those for the IP, EP(3) and FP, when examined by competitive reverse transcriptase-PCR. Those for the EP(1), EP(2) and DP, however, could not be detected. AE1-329, an EP(4) agonist, and cicaprost, an IP agonist, inhibited platelet derived growth factor (PDGF)-induced proliferation of VSMCs from wild-type mice; these inhibitory effects disappeared completely in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. In accordance with these effects, AE1-329 and cicaprost stimulated cAMP production in VSMCs from wild-type mice, which were absent in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. Effects of PGE(2) on cell proliferation and adenylate cyclase were almost similar with those of AE1-329 in VSMCs from wild-type mice, which disappeared in VSMCs from EP(4)(-/-) mice. PGD(2) inhibited PDGF-induced proliferation of VSMCs from both wild-type and DP(-/-) mice to a similar extent. This action of PGD(2) was also observed in VSMCs from EP4(-/-) and IP(-/-) mice. In VSMCs from wild-type mice, I-BOP, a TP agonist, showed potentiation of PDGF-induced hypertrophy. I-BOP failed to show this action in VSMCs from TP(-/-) mice. The specific agonists for the EP(1), EP(2) or EP(3), and PGF(2)alpha showed little effect on the growth of VSMCs. These results show that PGE(2), PGI(2) and TXA(2) modulate PDGF-induced proliferation or hypertrophy of VSMCs via the EP(4), IP and TP, respectively, and that the inhibitory effect of PGD(2) on PDGF-induced proliferation is not mediated by the DP, EP(4) or IP.
authors.affiliation: Department of Pharmacology, Asahikawa Medical College, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujino
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Yuhki
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hara
authors.forename: Osamu
authors.initials: O
authors.lastname: Takahata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okada
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Xiao
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Hideji
authors.initials: H
authors.lastname: Karibe
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwashima
authors.forename: Jun
authors.initials: J
authors.lastname: Fukuzawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hasebe
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ushikubi
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D017209:Apoptosis; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006984:Hypertrophy; D007930:Leucine / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D015230:Prostaglandin D2 / Q000494:pharmacology / Q000502:physiology; D011453:Prostaglandins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000172:deficiency / Q000235:genetics; D013936:Thymidine / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D011453:Prostaglandins; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D007930:Leucine; D015230:Prostaglandin D2; D013936:Thymidine