Cyclic AMP-induced inhibition of collagen lattice contraction by fibroblasts may be attenuated by both cyclic AMP dependent and independent mechanisms.

The contraction of collagen lattices made with foreskin fibroblasts in medium containing 1% fetal bovine serum was inhibited by intracellular cyclic AMP-raising drugs including cholera toxin (CT), forskolin, and dibutyryl-cAMP. The inhibition by CT was attenuated by insulin, acidic fibroblast growth factor (aFGF), and transforming growth factor-beta (TGF-beta). All three peptide factors have previously been reported to promote collagen lattice contraction by arterial smooth muscle cells and/or fibroblasts. Incubation of cells suspended in collagen gels with CT and forskolin resulted in a transient rise of the intracellular cyclic AMP levels, which peaked at 2 hr and 30 min, respectively, after drug exposure. Cholera toxin-induced intracellular cyclic AMP increase was attenuated by TGF-beta, but not by aFGF and insulin, when added simultaneously. Thus, TGF-beta may attenuate CT's inhibition on collagen lattice contraction by attenuating CT-induced intracellular cyclic AMP increase, whereas the attenuation by insulin and aFGF on the inhibition of lattice contraction may be mediated by a cyclic AMP-independent mechanism.