title: Regulation of human penile smooth muscle tone by prostanoid receptors.
abstract: 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.
authors.affiliation: Fundación para la Investigación y el Desarrollo en Andrología, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Angulo
authors.forename: Pedro
authors.initials: P
authors.lastname: Cuevas
authors.forename: Jose M
authors.initials: JM
authors.lastname: La Fuente
authors.forename: Jose M
authors.initials: JM
authors.lastname: Pomerol
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Castañé
authors.forename: Ana
authors.initials: A
authors.lastname: Puigvert
authors.forename: Sonia
authors.initials: S
authors.lastname: Gabancho
authors.forename: Argentina
authors.initials: A
authors.lastname: Fernández
authors.forename: Peter
authors.initials: P
authors.lastname: Ney
authors.forename: Iñigo
authors.initials: I
authors.lastname: Sáenz De Tejada
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000098:blood supply / Q000378:metabolism / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis* / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D014655:Vascular Resistance
chemical_list: D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D016718:Arachidonic Acid; D015237:Dinoprost; D000242:Cyclic AMP; D000527:Alprostadil