Abstract
In this study, we have characterized functional EP receptors in human corpus cavernosum (HCC) tissue and in HCC smooth muscle cells (SMC). Using RNase protection assays, we determined expression of EP2, EP3I and EP3II receptor mRNA. In organ bath preparations of HCC tissue strips, PGE1 caused dose-dependent relaxation at concentrations below 300 nM. At concentrations greater than 300 nM, PGE1 caused contraction. Addition of the EP1/EP2/EP3 receptor antagonist AH6809 inhibited this contraction and facilitated further relaxation through concentrations above 1 μM of PGE1. The EP1/EP3 receptor selective agonist 17-phenyltrinor-PGE2 caused dose-dependent contraction that was partially attenuated by SC51322, an EP1 selective antagonist. In cultures of HCC SMC, PGE1 stimulated cAMP accumulation in a dose-dependent manner. Interestingly, AH6809 significantly attenuated PGE1-induced cAMP accumulation. Sulprostone, a selective EP3 receptor agonist, induced weak contractions in HCC tissue strips but augmented forskolin-induced cAMP synthesis in HCC SMC. The data in this study suggest that HCC and cultured smooth muscle cells express EP1, EP2 and EP3 receptors. These receptors mediate their responses via different biochemical pathways and are expected to have different responses in regulating smooth muscle tone. Thus, we suggest that the ultimate response in erectile tissue to various prostanoids is the integration of responses elicited by individual EP receptor subtypes to a given ligand.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 8 print issues and online access
$259.00 per year
only $32.38 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Narumiya S, Sugimoto Y, Ushikubi F . Prostanoid receptors. Structure and function. Physiol Rev 1999; 79: 1193–1226.
Breyer RM, Bagdassarian CK, Myers SA, Breyer MD . Prostanoid receptors: subtypes and signaling. Ann Rev Pharmacol Toxicol 2001; 41: 661–690.
Pierce KL, Gil DW, Woodward DF, Regan JW . Cloning of human prostanoid receptors. Trends Pharmacol Sci 1995; 16: 1–22.
Roy AC, Tan SM, Kottegoda SR, Ratnam SS . Ability of human corpus cavernosum to generate prostaglandins and thromboxanes in vitro. IRCS Med Sci 1984; 12: 608.
Daley JT et al. Prostanoid production in rabbit corpus cavernosum. I. Regulation by oxygen tension. J Urol 1996; 155: 1482–1487.
Moreland RB et al. Oxygen-dependent prostanoid synthesis activates functional PGE receptors on human corpus cavernosum smooth muscle cells. Am J Physiol 2001; 281: H552–H557.
Hedlund H, Andersson KE . Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery. J Urol 1985; 134: 1245–1250.
Porst H . The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol 1996; 155: 802–815.
Moreland RB et al. Misoprostol induces relaxation of human corpus cavernosum smooth muscle: comparison to prostaglandin E1 . Int J Impot Res 2000; 12: 107–110.
Angulo J et al. Regulation of human penile smooth muscle tone by prostanoid receptors. Br J Pharmacol 2002; 136: 23–30.
Lue TF, Levine JD . Impotence. J Urol 1995; 155: 85.
Moreland RB et al. PGE1 suppresses the induction of collagen synthesis by transforming growth factor-β1 in human corpus cavernosum smooth muscle. J Urol 1995; 153: 826–834.
Traish AM, Palmer MA, Goldstein I, Moreland RB . Expression of functional muscarinic acetylcholine receptor subtypes in cultured human corpus cavernosum and in cultured smooth muscle cells. Receptors 1996; 5: 159–176.
Regan JW et al. Cloning of a novel human prostaglandin receptor with characteristics of the pharmacologically defined EP2 subtype. Mol Pharmacol 1994; 46: 213–220.
Adam M et al. Cloning and expression of three isoforms of the human EP3 prostanoid receptor. FEBS Lett 1994; 338: 170–174.
Abramovitz M et al. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta 2000; 1483: 285–293.
Kiriyama M et al. Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol 1997; 122: 217–224.
Jensen TJ, Nedergaard OA . Modulation of norepinephrine release from sympathetic neurons of the rabbit aorta by prejunctional prostanoid receptors. J Pharmacol Exp Ther 1999; 291: 7–11.
Allgaier C, Meder W . Cultured chick sympathetic neurons: prostanoid EP1 receptor-mediated facilitation of noradrenaline release. Naunyn Schmiedebergs Arch Pharmacol 1995; 352: 447–450.
Traish AM, Moreland RB, Huang YH, Goldstein I . Expression of functional alpha-2-adrenergic receptor subtypes in human corpus cavernosum and in human corpus cavernosum smooth muscle cells. Recept Signal Transduct 1997; 7: 55–67.
Traish AM et al. G-protein-coupled receptor agonists augment adenylyl cyclase activity induced by forskolin in human corpus cavernosum smooth muscle cells. Recept Signal Transduct 1997; 7: 123–134.
Andersson KE . Pharmacology of penile erection. Pharmacol Rev 2001; 53: 417–450.
Moreland RB, Hsieh GC, Nakane M, Brioni JD . The biochemical and neurologic basis for the treatment of erectile dysfunction. J Pharmacol Exp Ther 2001; 296: 225–234.
Minami T et al. L-NAME, an inhibitor of nitric oxide synthase, blocks the established allodynia induced by intrathecal administration of prostaglandin E2 . Neurosci Lett 1995; 201: 239–242.
Minami T et al. Characterization of EP receptor subtypes responsible for prostaglandin E2-induced pain responses by use of EP1 and EP3 receptor knockout mice. Br J Pharmacol 2001; 133: 438–444.
Stock JL et al. The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. J Clin Invest 2001; 107: 325–331.
Malmberg AB, Rafferty MF, Yaksh TL . Antinociceptive effect of spinally delivered prostaglandin E receptor antagonists in the formalin test on the rat. Neurosci Lett 1994; 173: 193–196.
Kim N, Azadzoi KM, Goldstein I, Saenz de Tejada I . A nitric oxide-like factor mediates nonadrenergic–noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 1991; 88: 112–118.
Berry JL et al. Inhibition by adrenergic neurone blocking agents of the relaxation induced by BRL 38227 in vascular, intestinal and uterine smooth muscle. Br J Pharmacol 1992; 107: 288–295.
Berry JL, Small RC, Foster RW . Tracheal relaxation induced by potassium channel opening drugs: its antagonism by adrenergic neurone blocking agents. Br J Pharmacol 1992; 106: 813–818.
Lee SW et al. Prostaglandin E1 activates the large-conductance KCa channel in human corporal smooth muscle cells. Int J Impot Res 1999; 11: 189–199.
Ungrin MD et al. Key structural features of prostaglandin E2 and prostanoid analogs involved in binding and activation of the human EP1 prostanoid receptor. Mol Pharmacol 2001; 59: 1446–1456.
Kawahara H et al. A prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) reduces hyperalgesia, allodynia, and c-fos gene expression in rats with chronic nerve constriction. Anesth Analg 2001; 93: 1012–1017.
Acknowledgements
We acknowledge the excellent technical assistance of Yue-hua Huang, Cynthia Gallant and Erika Liné as well as the administrative assistance of Jerie McGrath-Cerqua. This work was supported by Grants R29-DK47950, R01-DK39080, R01-DK40025 and K01-DK02696 from the National Institutes of Health.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Moreland, R., Kim, N., Nehra, A. et al. Functional prostaglandin E (EP) receptors in human penile corpus cavernosum. Int J Impot Res 15, 362–368 (2003). https://doi.org/10.1038/sj.ijir.3901042
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijir.3901042
Keywords
This article is cited by
-
Erectile dysfunction
Nature Reviews Disease Primers (2016)
-
The potent relaxant effect of resveratrol in rat corpus cavernosum and its underlying mechanisms
International Journal of Impotence Research (2013)
-
Role of Prostanoid Production and Receptors in the Regulation of Retinal Endogenous Amino Acid Neurotransmitters by 8-Isoprostaglandin E2, Ex Vivo
Neurochemical Research (2009)
-
Gene and protein expression profiles of prostaglandin E2 receptor subtypes in the human corpus cavernosum
International Journal of Impotence Research (2006)
-
In vitro models: research in physiology and pharmacology of the lower urinary tract
British Journal of Pharmacology (2006)