O2-dependent prostanoid synthesis activates functional PGE receptors on corpus cavernosum smooth muscle

Departments of 1 Urology, 2 Surgery, and 3 Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118 We have previously demonstrated that decreased O 2 tension inhibits prostaglandin synthesis from human corpus cavernosum smooth muscle cells in static culture over 8-18 h (R. B. Moreland et al., Molecular Urology 2: 41-47, 1998). In this report, an experimental system was designed that allowed determination of the effects of O 2 tension changes over the time frame of physiological penile erection. Human corpus cavernosum smooth muscle cells were cultured on microcarrier beads in enclosed stirrer flasks so that rapid changes of O 2 tension could be modulated. After 18 h of equilibration at 30-40 mmHg to simulate blood P O 2 at penile flaccidity, O 2 tension was increased to 100 mmHg for 1 h and then returned to 30-40 mmHg. Media samples were withdrawn for prostanoid synthesis and cell samples were taken for cAMP determinations. After 18 h of 30-40 mmHg P O 2 values, prostanoid synthesis by human corpus cavernosum smooth muscle cells was low (0.1-0.7 pmol/10 6 cells). When P O 2 was increased to 100 mmHg, a rapid increase in PGE 2 >> PGF 2 > PGD 2 was observed (thromboxane A 2 was undetectable), which peaked at 5.7 pmol PGE 2 /10 6 cells. Increased O 2 tension correlated with increased PGE 2 and increased intracellular synthesis of cAMP. The prostaglandin G/H synthase inhibitor indomethacin or the E prostanoid (EP 2 )-selective antagonist AH-6809 each inhibited the O 2 -tension-dependent increases in cAMP. These data support a role of differential O 2 tension in the penis in the smooth muscle synthesis of PGE 2 , which in turn increases cAMP synthesis via EP 2 receptors. tension; E prostanoid receptor; corpus cavernosum; erectile dysfunction