Cyclic AMP modulates TGF-beta 1-induced fibrillar collagen synthesis in cultured human corpus cavernosum smooth muscle cells.
OBJECTIVE
The mechanisms by which PGE1 suppresses transforming growth factor beta 1 (TGF-beta 1) induced fibrillar collagen synthesis in human corpus cavernosum smooth muscle cells (HCC SMC) remain undefined. Since PGE1 induces cyclic AMP (cAMP) synthesis in HCC SMC, the aim of this research is to investigate the role of cAMP in the regulation of connective tissue biosynthesis in human corporal smooth muscle cells in culture.


METHODS
HCC SMC were incubated for 24 h in media containing [3H] 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 determined by [3H]-proline incorporation into pepsin-resistant, trichloroacetic acid and precipitable protein.


RESULTS
TGF-beta 1-induced collagen synthesis in HCC SMC was inhibited by receptor-mediated (PGE1) and non-receptor-mediated (forskolin) increases in cAMP synthesis, as well as the cell-permeable analog, dibutyryl cAMP. Sodium nitroprusside, a nitric oxide donor, and the cell-permeable analog, dibutyryl cGMP had no effect on TGF-beta 1-induced collagen synthesis.


CONCLUSIONS
Cyclic AMP synthesis in HCC SMC inhibits TGF-beta 1-induced collagen synthesis. Agents which increase cAMP through specific G-protein-coupled receptors, direct stimulation of adenylate cyclase, or inhibition of phosphodiesterase activity could have beneficial effects as modulators of corpus cavernosum connective tissue biosynthesis.
Moreland
R B
RB
Department of Urology, Boston University School of Medicine, MA 02118, USA. moreland@bu.edu
Gupta
S
S
Goldstein
I
I
Traish
A
A
D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003238:Connective Tissue / Q000378:metabolism*; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D010413:Penis / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D003094:Collagen; D000242:Cyclic AMP