Regulation of human penile smooth muscle tone byprostanoid receptors

We have characterized the prostanoid receptors involved in the regulation of human penile arterial and trabecular smooth muscle tone. 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. TP‐receptors mediate contraction of HCCS and penile resistance arteries (HPRA), since the agonist of these receptors, U46619, potently contracted HCCS (EC 50 8.3±2.8 n M ) and HPRA (EC 50 6.2±2.2 n M ), and the contractions produced by prostaglandin F 2α at high concentrations (EC 50 6460±3220 n M in HCCS and 8900±6700 n M in HPRA) were inhibited by the selective TP‐receptor antagonist, SQ29548 (0.02 μ M ). EP‐receptors are responsible for prostanoid‐induced relaxant effects in HCCS because only prostaglandin E 1 (PGE 1 ), prostaglandin E 2 and the EP 2 /EP 4 ‐receptor agonist, butaprost, produced consistent relaxation of this tissue (EC 50 93.8±31.5, 16.3±3.8 and 1820±1284 n M , respectively). In HPRA, both prostacyclin and PGE 1 (EC 50 60.1±18.4 and 109.0±30.9 n M , respectively) as well as the selective IP receptor agonist, cicaprost, and butaprost (EC 50 25.2±15.2 and 7050±6020 n M , respectively) caused relaxation, suggesting co‐existence of IP‐ and EP‐receptors (EP 2 and/or EP 4 ). 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 EP 2 ‐ and/or EP 4 ‐receptors in HCCS and by EP‐ and IP‐receptors in HPRA.British Journal of Pharmacology (2002) 136 , 23–30; doi: 10.1038/sj.bjp.0704675