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 increse, whereas the attenuation by insulin and aFGF on the inhibition of lattice contraction may be mediated by a cyclic AMP-independent mechanism.