title: Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP.
abstract: The effects of cyclic nucleotides on elastin synthesis were studied in ligamentum nuchae fibroblasts by adding exogenous cyclic nucleotide derivatives or beta-adrenergic agents to cell culture medium. Elastin synthesis was enhanced (approximately 80%) by dibutyryl cGMP (Bt2cGMP) in concentrations ranging from 0.01 to 100 nM. Two other cGMP derivatives, 8-bromoguanosine 3':5'-cyclic monophosphate (8-Br-cGMP) and 2'-deoxy-cGMP, were also potent stimulators of elastin synthesis. In the absence of calcium, basal elastin production was substantially decreased (40% of control) and cGMP analogs no longer stimulated elastin synthesis, suggesting a role for calcium in the cGMP response. Bt2cAMP had no demonstrable effect on elastin production except at high concentrations which produced a nonspecific decrease equivalent to the decrease in total protein synthesis. Similarly, elevation of endogenous cellular cAMP levels by beta-adrenergic stimulation produced no change in elastin production. When 8-Br-cGMP was added to cells together with Bt2cAMP, cGMP-dependent stimulation of elastin production was abolished by cAMP in a dose-dependent fashion. These results suggest a coordinated means by which elastin production is controlled in ligament cells, i.e. increased cGMP levels lead to a stimulation of elastin production that is reversed by cAMP.
authors.forename: R P
authors.initials: RP
authors.lastname: Mecham
authors.forename: B D
authors.initials: BD
authors.lastname: Levy
authors.forename: S L
authors.initials: SL
authors.lastname: Morris
authors.forename: J G
authors.initials: JG
authors.lastname: Madaras
authors.forename: D S
authors.initials: DS
authors.lastname: Wrenn
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004549:Elastin / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008022:Ligaments / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; D004549:Elastin; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D002118:Calcium