Regulation of human penile smooth muscle tone by prostanoid receptors

1 We have characterized the prostanoid receptors involved in the regulation of human penile arterial and trabecular smooth muscle tone. 2 Arachidonic acid induced relaxation of human corpus cavernosum strips (HCCS) that was blocked by the cyclo-oxygenase inhibitor, indomethacin, and augmented by the thromboxane receptor (TP) antagonist, SQ29548, suggesting that endogenous production of prostanoids regulates penile smooth muscle tone. 3 TP-receptors mediate contraction of HCCS and penile resistance arteries (HPRA), since the agonist of these receptors. U46619, potently contracted HCCS (EC50 8.3 +/- 2.8 nM) and HPRA (EC50 6.2 +/- 2.2 nM), and the contractions produced by prostaglandin F-2alpha at high concentrations (EC50 6460 +/- 3220 nM in HCCS and 8900 +/- 6700 nM in HPRA) were inhibited by the selective TP-receptor antagonist, SQ29548 (0.02 muM). 4 EP-receptors are responsible for prostanoid-induced relaxant effects in HCCS because only prostaglandin E-1 (PGE(1)), prostaglandin E-2 and the EP2/EP4-receptor agonist, butaprost, produced consistent relaxation of this tissue (EC50) 93.8 +/- 31.5, 16.3 +/- 3.8 and 1820 +/- 1284 nM, respectively). In HPRA, both prostacyclin and PGE(1) (EC50) 60.1 +/- 18.4 and 109.0 +/- 30.9 nM, respectively) as well as the selective IP receptor agonist. cicaprost. and butaprost (EC50 25.2 +/- 5.2 and 7050 +/- 6020 nM, respectively) caused relaxation. suggesting co-existence of IP- and EP-receptors (EP- and or EP-). 5 In summary. endogenous production of prostanoids may regulate penile smooth muscle contractility by way of specific receptors. TP-receptors mediate contraction in HCCS and HPRA, while the relaxant effects of prostanoids are mediated by EP2- and/or EP4-receptors in HCCS and by EP- and IP-receptors in HPRA.