title: 5-HT2 receptor mRNA is overexpressed in cultured rat aortic smooth muscle cells relative to normal aorta.
abstract: Proliferation of smooth muscle cells in arteries is associated with contractile hypersensitivity to serotonin (5-HT). A possible explanation is that smooth muscle cells express increased numbers of phospholipase C (PLC)-coupled 5-HT receptors (5-HTR), which could mediate contractile and mitogenic signals via phosphatidylinositol turnover. To test this hypothesis, we performed a molecular characterization of 5-HTR subtypes in normal aorta and passaged rat aortic smooth muscle cells (RASM) in culture. Northern blot analysis revealed that growth-arrested cultured cells expressed 5-HT2R mRNA at 50-fold greater levels than aorta. 5-HT1CR mRNA was not detected in either case. 5-HT stimulated intracellular Ca2+ mobilization (fivefold peak increase) and c-fos mRNA induction (10-fold peak increase); both responses were strongly inhibited by selective 5-HT2R antagonists. Specific agonists for the 5-HT1AR, 5-HT1BR, and 5-HT1DR failed to induce c-fos mRNA. Although 5-HT (10 microM) increased [3H]thymidine incorporation (28% relative to 10% calf serum), it was a weak mitogen for cultured RASM based on cell counts. Thus there is high level expression of 5-HT2R mRNA by cultured RASM relative to aorta, and the 5-HT2R appears to be the only 5-HTR subtype mediating early growth signals in these cells. These data suggest that, following arterial injury in vivo, smooth muscle cells may overexpress the 5-HT2R, resulting in 5-HT contractile hypersensitivity and increased responsiveness to other growth factors.
authors.affiliation: Cardiology Division, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: M A
authors.initials: MA
authors.lastname: Corson
authors.forename: R W
authors.initials: RW
authors.lastname: Alexander
authors.forename: B C
authors.initials: BC
authors.lastname: Berk
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000235:genetics*; D012016:Reference Values; D012701:Serotonin / Q000494:pharmacology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin; D004247:DNA; D002118:Calcium