Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP.
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.
Mecham
R P
RP
Levy
B D
BD
Morris
S L
SL
Madaras
J G
JG
Wrenn
D S
DS
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
D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; D004549:Elastin; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D002118:Calcium