Regulation of human penile smooth muscle tone byprostanoid receptors

Abstract

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 (EC 50 8.3+2.8 nM) and HPRA (EC 50 6.2+2.2 nM), and the contractions produced by prostaglandin F 2a at high concentrations (EC 50 6460+3220 nM in HCCS and 8900+6700 nM in HPRA) were inhibited by the selective TP-receptor antagonist, SQ29548 (0.02 mM). 4 EP-receptors are responsible for prostanoid-induced relaxant e ects 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 nM, respectively). In HPRA, both prostacyclin and PGE 1 (EC 50 60.1+18.4 and 109.0+30.9 nM, respectively) as well as the selective IP receptor agonist, cicaprost, and butaprost (EC 50 25.2+15.2 and 7050+6020 nM, respectively) caused relaxation, suggesting co-existence of IP-and EP-receptors (EP 2 and/or EP 4 ).

Gene and protein expression profiles of prostaglandin E2 receptor subtypes in the human corpus cavernosum

“…11 Concerning expression of EP receptor in human corpus cavernosum, there are some previous reports using pharmacological method. Angulo et al 12 reported that EP2 receptor and/or EP4 receptor were related to relaxation of smooth muscle in human corpus cavernosum. In this pharmacological experiment, butaprost was used as the EP2 selective agonist by this study.…”

“…13 Therefore, it is not clear as to which one of EP receptor subtype (EP2 or EP4) works predominantly in relaxation of human corpus cavernosum by this report. 12 In addition to butaprost, sulprostone, which has agonistic activity for both EP1 and EP3, was used in this report, and did not lead to contraction of human corpus cavernosum. 12 Moreland et al 14 reported that human corpus cavernosum tissues and cultured smooth muscle cells express EP1, EP2 and EP3 receptors by RNase protection assay and pharmacological methods.…”

“…12 In addition to butaprost, sulprostone, which has agonistic activity for both EP1 and EP3, was used in this report, and did not lead to contraction of human corpus cavernosum. 12 Moreland et al 14 reported that human corpus cavernosum tissues and cultured smooth muscle cells express EP1, EP2 and EP3 receptors by RNase protection assay and pharmacological methods. They used several agonists for EP1 and/or EP3, and elicited only weak contraction of human corpus cavernosum tissues, and they have found the expression of EP2, EP3I and EP3II receptor mRNA.…”

Functional prostaglandin E (EP) receptors in human penile corpus cavernosum

“…6 Of these eicosanoids, only PGE 1 has been reported to relax penile cavernosal smooth muscle. [7][8][9][10] Further, arachidonic acid, the precursor of PGE 2 , can relax human corpus cavernosum (HCC) smooth muscle in the presence of thromboxane receptor antagonists, a process blocked by the prostaglandin G/H synthase inhibitor indomethacin. 10 Prostaglandin E can bind to several different subtypes of EP receptors.…”

“…[7][8][9][10] Further, arachidonic acid, the precursor of PGE 2 , can relax human corpus cavernosum (HCC) smooth muscle in the presence of thromboxane receptor antagonists, a process blocked by the prostaglandin G/H synthase inhibitor indomethacin. 10 Prostaglandin E can bind to several different subtypes of EP receptors. EP1 (Ga q11 -coupled) and EP3 (Ga i/ocoupled) receptors can potentially mediate trabecular smooth muscle contraction, while EP2 and EP4 (Ga s -coupled) may mediate trabecular smooth muscle relaxation via different signal transduction pathways.…”