O-2-dependent prostanoid synthesis activates functional PGE receptors on corpus cavernosum smooth muscle

We have previously demonstrated that decreased O-2 tension inhibits prostag landin 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, 19 98). In this report, an experimental system was designed that allowed deter mination of the effects of O-2 tension changes over the time frame of physi ological penile erection. Human corpus cavernosum smooth muscle cells were cultured on microcarrier beads in enclosed stirrer flasks so that rapid cha nges of O-2 tension could be modulated. After 18 h of equilibration at 30-4 0 mmHg to simulate blood P-O2 at penile flaccidity, O-2 tension was increas ed 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 Media samples were withdrawn for prostanoid synthesis and cell samples were taken for cAMP det erminations. After 18 h of 30-40 mmHg P-O2 values, prostanoid synthesis by human corpus cavernosum smooth muscle cells was low (0.1-0.7 pmol/10(6) cel ls). When P-O2 was increased to 100 mmHg, a rapid increase in PGE(2). PGF(2 alpha). PGD(2) was observed (thromboxane A(2) was undetectable), which pea ked at 5.7 pmol PGE(2)/10(6) cells. Increased O-2 tension correlated with i ncreased PGE(2) and increased intracellular synthesis of cAMP. The prostagl andin G/H synthase inhibitor indomethacin or the E prostanoid (EP2)-selecti ve 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 i n the smooth muscle synthesis of PGE(2), which in turn increases cAMP synth esis via EP2 receptors.