Modulation of collagen production by fibroblasts. Effects of chronic exposure to agonists that increase intracellular cyclic AMP

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Abstract
Cultured human lung fibroblasts were evaluated for their responsiveness to isoprenaline (isoproterenol) or prostaglandin[PG]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 cAMP. 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 cAMP. Cells incubated for 72 h with isoprenaline still responded to PGE2 when challenged for 6 h, however, when the order of agonist exposure was reversed, cells incubated with PGE2 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. Although cultured fibroblasts may become desensitized to 1 agonist, they may retain their sensitivity to 2nd agonist. Chronic suppression of collagen production may be achieved by alternate exposure to isoprenaline and PGE2.