CYCLIC-AMP MODULATES TGF-BETA(1)-INDUCED FIBRILLAR COLLAGEN-SYNTHESISIN CULTURED HUMAN CORPUS CAVERNOSUM SMOOTH-MUSCLE CELLS

Introduction and objectives: The mechanisms by which PGE(1) suppresses transforming growth factor beta(1) (TGF-beta(1)) induced fibrillar co llagen synthesis in human corpus cavernosum smooth muscle cells (HCC S MC) remain undefined. Since PGE(1) induces cyclic AMP (cAMP) synthesis in HCC SMC, the aim of this research is to investigate the role of cA MP in the regulation of connective tissue biosynthesis in human corpor al smooth muscle cells in culture. Materials and methods: HCC SMC were incubated for 24 h in media containing [H-3] proline with and without TGF-beta(1) in the presence or absence of agents which modulate cAMP or cGMP synthesis, or hydrolysis, Fibrillar collagen synthesis was det ermined by [H-3]-proline incorporation into pepsin-resistant, trichlor oacetic acid and precipitable protein. Results: TGF-beta(1)-induced co llagen synthesis in HCC SMC was inhibited by receptor-mediated (PGE(1) ) and non-receptor-mediated (forskolin) increases in cAMP synthesis, a s well as the cell-permeable analog, dibutyryl cAMP. Sodium nitropruss ide, a nitric oxide donor, and the cell-permeable analog, dibutyryl cG MP had no effect on TGF-beta(1)-induced collagen synthesis. Conclusion s: Cyclic AMP synthesis in HCC SMC inhibits TGF-beta(1)-induced collag en synthesis. Agents which increase cAMP through specific G-protein-co upled receptors, direct stimulation of adenylate cyclase, or inhibitio n of phosphodiesterase activity could have beneficial effects as modul ators of corpus cavernosum connective tissue biosynthesis.