title: Modulation of collagen production by fibroblasts. Effects of chronic exposure to agonists that increase intracellular cyclic AMP.
abstract: Cultured human lung fibroblasts were evaluated for their responsiveness to isoprenaline (isoproterenol) or prostaglandin E2 before and after chronic incubation with the agonist. Cells incubated for 6 h with either agonist were suppressed in terms of collagen production and exhibited increased intracellular cyclic AMP. Cells incubated for 72 h with the agonist and then re-challenged for 6 h with the same agonist did not demonstrate suppressed collagen production or increased cyclic AMP. Cells incubated for 72 h with isoprenaline still responded to prostaglandin E2 when challenged for 6 h; however, when the order of agonist exposure was reversed, cells incubated with prostaglandin E2 did not respond to a challenge by isoprenaline. If cells were allowed to recover for 48 h without the agonist after a 72 h chronic incubation, they recovered their responsiveness to the agonist. The results indicate that, although cultured fibroblasts may become desensitized to one agonist, they may retain their sensitivity to a second agonist and chronic suppression of collagen production may be achieved by alternate exposure to isoprenaline and prostaglandin E2.
mesh_terms: D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D011458:Prostaglandins E; D003094:Collagen; D000242:Cyclic AMP; D015232:Dinoprostone; D007545:Isoproterenol