Mechanistic insights into the role of α1-adrenergic receptors in lower urinary tract symptoms

Current Urology Reports

Volumn 5, Issue 4, 2004, Pages 258-266

  Michelotti, Gregory A ^a   Schwinn, Debra A ^b  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b NONE

Author keywords

Benign Prostatic Hyperplasia; Bladder Outlet Obstruction; Finasteride; Irritative Symptom; Lower Urinary Tract Symptom

Indexed keywords

ALPHA 1 ADRENERGIC RECEPTOR; ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT;

AGED; ANIMAL; BLADDER OBSTRUCTION; DISEASE MODEL; DRUG ANTAGONISM; HUMAN; MIDDLE AGED; PATHOPHYSIOLOGY; PHYSIOLOGY; RAT; REVIEW; SIGNAL TRANSDUCTION; URINARY TRACT DISEASE;

ADRENERGIC ALPHA-ANTAGONISTS; AGED; AGED, 80 AND OVER; ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; MIDDLE AGED; RATS; RECEPTORS, ADRENERGIC, ALPHA-1; SIGNAL TRANSDUCTION; URINARY BLADDER NECK OBSTRUCTION; UROLOGIC DISEASES;

EID: 16544366126     PISSN: 15272737     EISSN: 15346285     Source Type: Journal    
DOI: 10.1007/s11934-004-0048-0     Document Type: Article

References (78)

1. Boyle P, Robertson C, Mazzetta C, et al.: The prevalence of lower urinary tract symptoms in men and women in four centres: the UrEpik study. BJU Int 2003, 92:409–414. DOI: 10.1046/j.1464-410X.2003.04369.x
2. Committee APG: Benign prostatic hyperplasia: guideline on the management of benign prostatic hyperplasia. J Urol 2003, 170:530–547. DOI: 10.1097/01.ju.0000078083.38675.79
3. Rees RW, Foxwell NA, Ralph DJ, et al.: Y-27632, a Rho-kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cells. J Urol 2003, 170:2517–2522. DOI: 10.1097/01.ju.0000085024.47406.6c
4. Schwinn DA, Michelotti GA: Alpha1-adrenergic receptors in the lower urinary tract and vascular bed: potential role for the alpha1d subtype in filling symptoms and effects of ageing on vascular expression. BJU Int 2000, 85(suppl 2):6–11. DOI: 10.1046/j.1464-410X.2000.00061.x
5. MacDonald D, McNicholas TA: Drug treatments for lower urinary tract symptoms secondary to bladder outflow obstruction: focus on quality of life. Drugs 2003, 63:1947–1962. DOI: 10.2165/00003495-200363180-00004
6. Andersson KE: Storage and voiding symptoms: pathophysiologic aspects. Urology 2003, 62:3–10. DOI: 10.1016/j.urology.2003.09.030
7. Roehrborn CG, McConnell JD, Saltzman B, et al.: Storage (irritative) and voiding (obstructive) symptoms as predictors of benign prostatic hyperplasia progression and related outcomes. Eur Urol 2002, 42:1–6. DOI: 10.1016/S0302-2838(02)00210-5
8. Blue D, Zinner N, Grino P, et al.: Ro700004, a selective a1phaadrenoceptor antagonist, does not improve lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol 2002, 167:265A. DOI: 10.1016/S0022-5347(05)65444-4
9. Nickel JC: The use of alpha1-adrenoceptor antagonists in lower urinary tract symptoms: beyond benign prostatic hyperplasia. Urology 2003, 62:34–41. DOI: 10.1016/S0090-4295(03)00472-2
10. Djavan B, Shariat S, Fakhari M, et al.: Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia: a randomized, prospective clinical trial. Urology 1999, 53:251–259. DOI: 10.1016/S0090-4295(98)00538-X
11. Hampel C, Dolber P, Savic S, et al.: Changes in alpha-1 adrenergic receptor subtype gene expression during bladder outlet obstruction of rats [Abstract #2290]. J Urol 2004, in press.
12. Malloy B, Price D, Price R, et al.: alpha-1-adrenergic receptor subtypes in human detrusor. J Urol 1998, 160:937–943. DOI: 10.1016/S0022-5347(01)62836-2
13. Steers WD, Barrett DM, Wein AJ: Voiding dysfunction: diagnosis, classification, and management. In Adult and Pediatric Urology, edn 3. Edited by Gillenwater JY, Grayhack JT, Howards SS, Duckett JW. St. Louis: Mosby-Year Book, Inc; 1996:1220–1325.
14. Seaman E, Jacobs B, Blaivas J, Kaplan S: Persistence or recurrence of symptoms after transurethral resection of the prostate: a urodynamic assessment. J Urol 1994, 152:935–937.
15. Lepor H, Williford WO, Barry MJ, et al.: The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med 1996, 335:533–539. DOI: 10.1056/NEJM199608223350801
16. Michelotti G, Price D, Schwinn D: Alpha-1 adrenergic receptor regulation: basic science and clinical implications. Pharmacol Ther 2000, 83:281–309. DOI: 10.1016/S0163-7258(00)00092-9
17. Price D, Schwinn D, Lomasney J, et al.: Identification, quantification, and localization of mRNA for three distinct a1-adrenergic receptor subtypes in human prostate. J Urol 1993, 150:546–551.
18. Forray C, Bard J, Wetzel J, et al.: The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol 1994, 45:703–708.
19. Blue DJ, Grino P, Jung D, et al.: Evaluation of Ro 70-0004, a selective alpha-adrenoceptor antagonist, in men with benign prostatic hyperplasia. Proceedings from the 5th International Consultation on BPH (WHO sponsored). Paris: June 25–28, 2000.
20. Djavan B, Marberger M: A meta-analysis on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol 1999, 36:1–13. DOI: 10.1159/000019919
21. Guthrie R, Siegel R: A multicenter, community-based study of doxazosin in the treatment of concomitant hypertension and symptomatic benign prostatic hyperplasia: the Hypertension and BPH Intervention Trial (HABIT). Clin Ther 1999, 21:1732–1748. DOI: 10.1016/S0149-2918(99)80052-6
22. Kirby R: Expanding role of alpha adrenoceptor blockade in the treatment of benign prostatic hyperplasia. Int J Clin Pract 1998, 52:402–407.
23. Kumar V, Dewan S: Alpha adrenergic blockers in the treatment of benign hyperplasia of the prostate. Int Urol Nephrol 2000, 32:67–71. DOI: 10.1023/A:1007108201320
24. Michel MC, Taguchi K, Schafers RS, et al.: Alpha 1-adrenoceptor subtypes in the human cardiovascular and urogenital systems. Adv Pharmacol 1998, 42:394–398. DOI: 10.1016/S1054-3589(08)60772-3
25. Stafford-Smith M, Schambra U, Wilson K: a1-Adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding a1-adrenergic receptor subtypes at four distinct levels. Mol Brain Res 1998, 63:254–261. DOI: 10.1016/S0169-328X(98)00287-3
26. Steers WD, De GW: Effect of bladder outlet obstruction on micturition reflex pathways in the rat. J Urol 1988, 140:864–871.
27. Steers WD, Albo M, Tuttle JB: Calcium channel antagonists prevent urinary bladder growth and neuroplasticity following mechanical stress. Am J Physiol 1994, 266:R20-R26.
28. Zderic SA, Wein A, Rohrman D, et al.: Mechanisms of bladder smooth-muscle hypertrophy and decompensation: lessons from normal development and the response to outlet obstruction. World J Urol 1998, 16:350–358. DOI: 10.1007/s003450050079
29. Gosling J, Chilton C: The anatomy of the bladder, urethra, and pelvic floor. In Urodynamics: Principles, Practice, and Applications. Edited by Mundy A, Stephenson T, Wein A. London: Churchill Livingstone; 1984:3–13.
30. Nomiya M, Yamaguchi O: A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders. J Urol 2003, 170:649–653. The author’s work suggests a potentially important functional role for â3ARs in human bladder function. DOI: 10.1097/01.ju.0000067621.62736.7c
31. Walden PD, Gerardi C, Lepor H: Localization and expression of the alpha1A-1, alpha1B and alpha1D-adrenoceptors in hyperplastic and non-hyperplastic human prostate. J Urol 1999, 161:635–640. DOI: 10.1016/S0022-5347(01)61986-4
32. Nasu K, Moriyama N, Kawabe K, et al.: Quantification and distribution of alpha 1-adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non-hypertrophied tissue. Br J Pharmacol 1996, 119:797–803.
33. Moriyama N, Kurimoto S, Horie S, et al.: Detection of alpha 1-adrenoceptor subtypes in human hypertrophied prostate by in situ hybridization. Histochem J 1996, 28:283–288. DOI: 10.1007/BF02409016
34. Schwinn DA, Michelotti GA: Alpha1-adrenergic receptors in the lower urinary tract and vascular bed: potential role for the alpha1d subtype in filling symptoms and effects of ageing on vascular expression. BJU Int 2000, 85(suppl 2):6–11. DOI: 10.1046/j.1464-410X.2000.00061.x
35. Zderic SA, Levin RM, Wein AJ: Voiding function: relevant anatomy, physiology, pharmacology, and molecular aspects. In Adult and Pediatric Urology, edn 3. Edited by Gillenwater JY, Grayhack JT, Howards SS, Duckett JW. St. Louis: Mosby-Year Book, Inc.; 1996:1159–1219.
36. Gosling JA, Dixon JS: Detrusor morphology in relation to bladder outflow obstruction and instability. In Benign Prostatic Hypertrophy. Edited by Hinman F. Berlin: Springer-Verlag; 1983:666–671.
37. Lepor H, Zhang W, Kobayashi S, et al.: A comparison of the binding and functional properties of alpha-1 adrenoceptors and area density of smooth muscle in the human, canine. J Pharmacol Expt Ther 1994, 270:722–727.
38. Walden PD, Durkin MM, Lepor H, et al.: Localization of mRNA and receptor binding sites for the alpha 1a-adrenoceptor subtype in the rat, monkey, and human urinary bladder and prostate. J Urol 1997, 155:534A.
39. Shapiro RE, Winters B, Hales M, et al.: Endogenous circulating sympatholytic factor in orthostatic intolerance. Hypertension 2000, 36:553–560.
40. Stafford-Smith M, Schambra U, Wilson K, et al.: a2-Adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding a2-adrenergic receptor subtypes at four distinct levels. Mol Brain Res 1996, 34:109–117. DOI: 10.1016/0169-328X(95)00148-L
41. Stafford-Smith M, Shambra U, Wilson K, et al.: a1-Adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding alpha 1-adrenergic subtypes at four distinct levels. Mol Brain Res 1999, 63:254–261. DOI: 10.1016/S0169-328X(98)00287-3
42. Yamamoto T, Ghosh R, de Groat W, Somogyi G: Facilitation of transmitter release in the urinary bladders of neonatal and adult rats via alpha(1)-adrenoceptors. Eur J Pharmacol 2001, 414:31–35. DOI: 10.1016/S0014-2999(01)00769-5
43. Ordway G, Kolta M, Gerald M, Wallace LJ: Age-related change in a-adrenergic responsiveness of the urinary bladder of the rat is regionally specific. Neuropharmacology 1986, 25:1335–1340. DOI: 10.1016/0028-3908(86)90105-X
44. Schwinn DA, Johnson GI, Page SO, et al.: Cloning and pharmacological characterization of human alpha1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exper Ther 1995, 272:134–142.
45. Hampel C, Dolber P, Smith M, et al.: Modulation of a1-adrenergic receptor subtype expression by bladder outlet obstruction. J Urol 2002, 167:1513–1521. This work suggests that á1AR subtype switching occurs with the onset of bladder pathology and suggests an important role for the á1dAR in bladder dysfunction. DOI: 10.1016/S0022-5347(05)65355-4
46. Szell E, Yamamoto T, de Groat W, Somogyi G: Smooth muscle and parasympathetic nerve terminals in the rat urinary bladder have different subtypes of alpha(1) adrenoceptors. Br J Pharmacol 2000, 130:1685–1691. DOI: 10.1038/sj.bjp.0703475
47. Andersson KE: Alpha-adrenoceptors and benign prostatic hyperplasia: basic principles for treatment with alphaadrenoceptor antagonists. World J Urol 2002, 19:390–396.
48. Thor K, Hampel C, Schwinn D, Dolber P: Sympathetic control of obstructed bladder [Abstract 629]. Neuroscience 2000, 26:17.
49. Restorick J, Mundy A: The density of cholinergic and alpha and beta adrenergic receptors in the normal and hyperreflexic human detrusor. Br J Urol 1989, 63:32–35.
50. Andersson KE: Alpha 1-adrenoceptors and bladder function. Eur Urol 1999, 36:96–102. DOI: 10.1159/000052328
51. Spitsbergen JM, Clemow DB, McCarty R, et al.: Neurally mediated hyperactive voiding in spontaneously hypertensive rats. Brain Res 1998, 790:151–159. DOI: 10.1016/S0006-8993(98)00061-4
52. Steers W, Clemow D, Persson K, et al.: The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males. Exp Physiol 1999, 84:137–147.
53. Clemow D, Steers W, McCarty R, Tuttle J: Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Physiol 1998, 275:R1279-R1286.
54. Clemow D, Spitsbergen J, McCarty R, et al.: Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999, 161:1372–1377. DOI: 10.1016/S0022-5347(01)61686-0
55. O’Leary MP: Lower urinary tract symptoms/benign prostatic hyperplasia: maintaining symptom control and reducing complications. Urology 2003, 62:15–23. DOI: 10.1016/S0090-4295(03)00480-1
56. Barki-Harrington L, Luttrell LM, Rockman HA: Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist: a functional role for receptor-receptor interaction in vivo. Circulation 2003, 108:1611–1618. Although not directly related to LUTS, this paper represents an important paradigm of direct interactions between receptor systems that show antagonism of one receptor system directly modulates signaling of separate receptors. DOI: 10.1161/01.CIR.0000092166.30360.78
57. Kester RR, Mooppan UM, Gousse AE, et al.: Pharmacological characterization of isolated human prostate. J Urol 2003, 170:1032–1038. DOI: 10.1097/01.ju.0000080440.74266.b1
58. Cirino G, Sorrentino R, di Villa Bianca R, et al.: Involvement of beta 3-adrenergic receptor activation via cyclic GMP- but not NO-dependent mechanisms in human corpus cavernosum function. Proc Natl Acad Sci U S A 2003, 100:5531–5536. This paper shows an interaction between â3ARs and á1ARs, which potentially is very important based on the distribution and functional studies shown in human bladder by our laboratory and Nomiya and Yamaguchi. DOI: 10.1073/pnas.0931347100
59. Bratslavsky G, Kogan BA, Matsumoto S, et al.: Reperfusion injury of the rat bladder is worse than ischemia. J Urol 2003, 170:2086–2090. The Levin laboratory has published seminal work on the quantification of ischemia and hypoxia and its subsequent role in bladder dysfunction. This work was performed in rat and rabbit model systems. DOI: 10.1097/01.ju.0000092144.48045.13
60. Levin R, Haugaard N, O’Connor L, et al.: Obstructive response of human bladder to BPH vs rabbit bladder response to partial outlet obstruction: a direct comparison. Neurourol Urodyn 2000, 19:609–629. DOI: 10.1002/1520-6777(2000)19:5<609::AID-NAU7>3.0.CO;2-H
61. Levin RM, Levin SS, Zhao Y, Buttyan R: Cellular and molecular aspects of bladder hypertrophy. Eur Urol 1997, 32:15–21.
62. Shabsigh A, Hayek O, Weiner D, et al.: Acute increase in blood flow to the rat bladder subsequent to partial bladder outlet obstruction. Neurourol Urodyn 2000, 19:195–208. DOI: 10.1002/(SICI)1520-6777(2000)19:2<195::AID-NAU10>3.0.CO;2-L
63. Nigro DA, Haugaard N, Wein AJ, Levin RM: Metabolic basis for contractile dysfunction following chronic partial bladder outlet obstruction in rabbits. Mol Cell Biochem 1999, 200:1–6. DOI: 10.1023/A:1006973412237
64. Schroder A, Kogan B, Lieb J, Levin R: Increased blood flow after catheterization and drainage in the chronically obstructed rabbit urinary bladder. Urology 2001, 58:295–300. DOI: 10.1016/S0090-4295(01)01142-6
65. Ghafar M, Shabsigh A, Chichester P, et al.: Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol 2002, 167:1508–1512. DOI: 10.1016/S0022-5347(05)65354-2
66. Nozaki K, Tomizawa K, Yokoyama T, et al.: Calcineurin mediates bladder smooth muscle hypertrophy after bladder outlet obstruction. J Urol 2003, 170:2077–2081. DOI: 10.1097/01.ju.0000081460.23737.63
67. Brodde OE, Michel MC: Adrenergic and muscarinic receptors in the human heart [Process citation]. Pharmacol Rev 1999, 51:651–690.
68. Keffel S, Alexandrov A, Goepel M, Michel M: a1-Adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells. Biochem Biophys Res Comm 2000, 272:906–911. DOI: 10.1006/bbrc.2000.2850
69. Shibata K, Katsuma S, Koshimizu T, et al.: alpha 1-Adrenergic receptor subtypes differentially control the cell cycle of transfected CHO cells through a cAMP-dependent mechanism involving p27Kip1. J Biol Chem 2003, 278:672–678. DOI: 10.1074/jbc.M201375200
70. McConnell JD, Roehrborn CG, Bautista OM, et al.: The longterm effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003, 349:2387–2398. Although use of dual therapy is questionable based on results of the Prostate Cancer Prevention Trial, which revealed an unexpected increased risk of high-grade prostate cancer during finasteride therapy, the encouraging results reported by this study show the need for additional studies to determine the risks of finasteride therapy DOI: 10.1056/NEJMoa030656
71. Kyprianou N, Benning CM: Suppression of human prostate cancer cell growth by alpha1-adrenoceptor antagonists doxazosin and terazosin via induction of apoptosis. Cancer Res 2000, 60:4550–4555.
72. Kyprianou N, Chon J, Benning CM: Effects of alpha(1)-adrenoceptor (alpha(1)-AR) antagonists on cell proliferation and apoptosis in the prostate: therapeutic implications in prostatic disease. Prostate Suppl 2000, 9:42–46. DOI: 10.1002/1097-0045(2000)45:9+<42::AID-PROS9>3.0.CO;2-U
73. Kyprianou N: Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance. J Urol 2003, 169:1520–1525. DOI: 10.1097/01.ju.0000033280.29453.72
74. Kyprianou N, Jacobs SC: Induction of apoptosis in the prostate by alpha1-adrenoceptor antagonists: a novel effect of “old” drugs. Curr Urol Rep 2000, 1:89–96.
75. Erdogru T, Ciftcioglu MA, Emreoglu I, et al.: Apoptotic and proliferative index after alpha-1-adrenoceptor antagonist and/or finasteride treatment in benign prostatic hyperplasia. Urol Int 2002, 69:287–292. DOI: 10.1159/000066120
76. Thebault S, Roudbaraki M, Sydorenko V, et al.: Alpha1-adrenergic receptors activate Ca(2+)-permeable cationic channels in prostate cancer epithelial cells. J Clin Invest 2003, 111:1691–1701. DOI: 10.1172/JCI200316293
77. Preston A, Haynes JM: Alpha 1-adrenoceptor effects mediated by protein kinase C alpha in human cultured prostatic stromal cells. Br J Pharmacol 2003, 138:218–224. DOI: 10.1038/sj.bjp.0705021
78. Berger AP, Kofler K, Bektic J, et al.: Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia. Prostate 2003, 57:57–65. DOI: 10.1002/pros.10279