Angulo Javier, Cuevas Pedro, La Fuente Jose M, Pomerol Jose M, Ruiz-Castañé Eduardo, Puigvert Ana, Gabancho Sonia, Fernández Argentina, Ney Peter, Sáenz De Tejada Iñigo
Fundación para la Investigación y el Desarrollo en Andrología, Madrid, Spain.
Br J Pharmacol. 2002 May;136(1):23-30. doi: 10.1038/sj.bjp.0704675.
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 (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 microM). EP-receptors are responsible for prostanoid-induced relaxant effects in HCCS because only prostaglandin E1 (PGE1), prostaglandin E2 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 PGE1 (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+/-15.2 and 7050+/-6020 nM, respectively) caused relaxation, suggesting co-existence of IP- and EP-receptors (EP2 and/or EP4). 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.
我们已经明确了参与调节人阴茎动脉和小梁平滑肌张力的前列腺素受体。花生四烯酸可诱导人海绵体条（HCCS）舒张，该舒张作用被环氧化酶抑制剂吲哚美辛阻断，并被血栓素受体（TP）拮抗剂SQ29548增强，这表明前列腺素的内源性产生调节阴茎平滑肌张力。TP受体介导HCCS和阴茎阻力动脉（HPRA）的收缩，因为这些受体的激动剂U46619能有效收缩HCCS（EC50 8.3±2.8 nM）和HPRA（EC50 6.2±2.2 nM），且高浓度前列腺素F（2α）产生的收缩（HCCS中EC50 6460±3220 nM，HPRA中EC50 8900±6700 nM）被选择性TP受体拮抗剂SQ29548（0.02 μM）抑制。EP受体负责前列腺素在HCCS中诱导的舒张作用，因为只有前列腺素E1（PGE1）、前列腺素E2和EP2/EP4受体激动剂布他前列素能使该组织产生持续的舒张（EC50分别为93.8±31.5、16.3±3.8和1820±1284 nM）。在HPRA中，前列环素和PGE1（EC50分别为60.1±18.4和109.0±30.9 nM）以及选择性IP受体激动剂西卡前列素和布他前列素（EC50分别为25.2±15.2和7050±6020 nM）均引起舒张，提示IP和EP受体（EP2和/或EP4）共存。总之，前列腺素的内源性产生可能通过特定受体调节阴茎平滑肌收缩性。TP受体介导HCCS和HPRA的收缩，而前列腺素的舒张作用在HCCS中由EP2和/或EP4受体介导，在HPRA中由EP和IP受体介导。
