O2-dependent prostanoid synthesis activates functional PGE receptors on corpus cavernosum smooth muscle.
We have previously demonstrated that decreased O2 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 O2 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 O2 tension could be modulated. After 18 h of equilibration at 30-40 mmHg to simulate blood PO2 at penile flaccidity, O2 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 Media samples were withdrawn for prostanoid synthesis and cell samples were taken for cAMP determinations.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 PO2 values, prostanoid synthesis by human corpus cavernosum smooth muscle cells was low (0.1-0.7 pmol/10(6) cells). When PO2 was increased to 100 mmHg, a rapid increase in PGE2 >> PGF2alpha > PGD2 was observed (thromboxane A2 was undetectable), which peaked at 5.7 pmol PGE2/10(6) cells. Increased O2 tension correlated with increased PGE2 and increased intracellular synthesis of cAMP. The prostaglandin G/H synthase inhibitor indomethacin or the E prostanoid (EP2)-selective antagonist AH-6809 each inhibited the O2-tension-dependent increases in cAMP. These data support a role of differential O2 tension in the penis in the smooth muscle synthesis of PGE2, which in turn increases cAMP synthesis via EP2 receptors.
Moreland
R B
RB
Department of Urology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. robert.moreland@ln.ssw.abbott.com
Albadawi
H
H
Bratton
C
C
Patton
G
G
Goldstein
I
I
Traish
A
A
Watkins
M T
MT
D019898:Autocrine Communication; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D010413:Penis; D011453:Prostaglandins / Q000096:biosynthesis*; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D015398:Signal Transduction
D011453:Prostaglandins; D018078:Receptors, Prostaglandin E; D010100:Oxygen