245
Physiology and PharMacology of thE ProstatE
less selective for this receptor (alfuzosin) cause |
Summary |
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fewer changes in seminal emission and ejacula- |
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tion than tamsulosin.92 |
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The prostate is an exocrine gland that manufac- |
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For large prostates with increasing likelihood |
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tures an array of substances postulated to play a |
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of future urinary retention, hematuria or surgi- |
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role in fertility or host defenses. Prostate growth, |
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cal intervention, especially voiding symptoms |
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development of BPH and cancer is attributed to |
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(slow stream, hesitancy, dribbling, and double |
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stromal–epithelial |
interactions |
mediated |
by |
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voiding) the 5AR inhibitors (finasteride, dutas- |
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cell–cell interactions via integrins and cadherins |
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teride) are reasonable drugs to treat LUTS in |
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as well as a wide range of growth factors and |
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men with large |
prostates. These agents take |
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hormones. Growth factors and other substances |
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3–6 months |
to |
achieve |
maximal |
benefit. |
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produced by the prostate are likely to influence |
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Additional benefits include reduction in hema- |
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neural |
growth, morphology, |
and |
transmitter |
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turia and a suggested reduction in prostate can- |
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expression, and |
function in an |
autocrine/ |
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cer.93,94 5AR inhibition causes a rapid reduction |
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paracrine-like fashion. The most important of |
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in vascular endothelial growth factor (VEGF) |
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these |
is |
DHT. This observation |
has |
been |
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which may explain the reduction in hematuria. |
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exploited to develop drugs that block the pro- |
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The magnitude of clinical benefits of both 5AR |
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duction |
of DHT, |
namely, |
5AR |
inhibitors, |
to |
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inhibitors is similar.95,96 However, dutasteride |
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shrink the prostate and relieve symptoms of |
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has the theoretical advantage in possible greater |
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BPH. Whether this class of drugs can be used to |
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prophylaxis against prostate cancer and slightly |
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prevent the development of adenocarcinoma of |
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more rapid onset by virtue of blockade of both |
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the prostate is hotly debated. |
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types I and II AR compared to finasteride, which |
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The prostate receives input from sympathetic |
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only acts on type II AR. Ongoing clinical trials |
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and to a lesser extent parasympathetic nerves. |
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are investigating these assertions. |
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In contrast to other genitourinary tissues, post- |
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Several large |
trials (PREDICT, VA |
CoOP, |
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ganglionic cholinergic sympathetic nerves are |
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MTOPS) have shown the benefit of combination |
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responsible for secretion while postganglionic |
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therapy with a-adrenergic antagonists and 5AR |
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noradrenergic sympathetic nerves mediate con- |
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inhibitors (doxzasosin/finasteride, terazosin/ |
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traction in this organ and the urethra as well as |
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finasteride, alfuzosin/dutasteride).97-100 Often α |
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bladder neck via a and a |
receptors, respec- |
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blockers can be withdrawn in patients on com- |
tively. This latter |
1A |
1D |
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the principal |
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bination therapy |
and symptomatic improve- |
finding |
forms |
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basis for use of a blockers in men with LUTS |
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ment persists. |
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due to BPH. Recent data suggesting that PDE5 |
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If men complaining of predominately storage |
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inhibitors may also be effective for the treat- |
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symptoms,especially urge urinary incontinence, |
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ment of LUTS due to BPH could be due to aug- |
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have low PSAs (<1.5 ng/mL) and small prostates |
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mentation of NO production and release from |
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on digital rectal examination, antimuscarinics |
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nerves in the prostatic stroma and urethra. |
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may be a good choice alone or in combination |
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Improvement in LUTS following injection of |
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with an a-adrenergic antagonist. Because trials |
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botulinum toxin into the prostate is proof of the |
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excluded men |
with postvoid residual |
urines |
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principle |
that abolishing |
neural |
input |
to |
the |
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greater than 150 mL, limiting the use of anti- |
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prostate reduces LUTS almost to the degree seen |
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muscarinics if the patient has a high residual is |
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with surgery. Exploitation of these findings to |
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prudent. If the patient has cognitive dysfunction |
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further enhance BPH therapy is likely. |
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antimuscarinics should probably not be |
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initiated. |
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If a patient has erectile dysfunction plus |
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LUTS,an a-adrenergic antagonist (tamsulosin) |
References |
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combined with daily PDE 5 inhibitor (tadala- |
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fil) is reasonable. If ejaculatory dysfunction |
1. Meares EM. Prostatitis. Med Clin North Am. 1991;75: |
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occurs (up to 20%) then switching to alfuzosin |
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can be considered. The use of 5AR inhibitors, |
405-424 |
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2. Veltri R, Rodriguez R, et al. Molecular biology, endo- |
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which can cause erectile |
dysfunction and |
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crinology, and physiology of the prostate and semi- |
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reductions in ejaculate volume should be lim- |
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nal vesicles. In: Wein AJ, ed. Campell-Walsh Urology. |
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ited as well. |
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9th ed. Philadelphia: Saunders; 2007:chap 85 |
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246
Practical Urology: EssEntial PrinciPlEs and PracticE
3.Partanen M, Hervonen A. The effect of long-term castration on the histochemically demonstrable cate-
cholamines in the hypogastric ganglion of the rat.
J Autonom Nerv Syst. 1979;1:139-147
4.Shapiro E, Miller A, Lepor H. Down regulation of the muscarinic cholinergic receptor of the rat prostate following castration. J Urol. 1985;134(1):179-182
5.Melvin J, Hamill R. The major pelvic ganglion: androgen control of postnatal development. J Neurosci. 1987;7(6): 1607-1612
6.Hamill R, Schroeder B. Hormonal regulation of adult sympathetic neurons: the effects of castration on neuropeptide Y, norepinephrine, and tyrosine hydroxylase activity. J Neurobiol. 1990;21(5):731-742
7.Regunathan S, Nassir Y, Sundaram K, et al. Expression of
I2-Imidazoline sites in rat prostate. Effect castration aging. Biochem Pharmacol. 1996;51:455-459
8.Farnsworth W, Lawrence M. Regulation of prostate secretion in the rat. Am J Physiol. 1965;119:373-376
9.Bodansky M, Sharaf H, Roy J, et al. Contractile activity of vasotocin, oxytocin, and vasopressin on mammalian prostate. Eur J Pharmacol. 1992;216:311-313
10.Sharaf H, Foda HD, Said SI, et al. Oxytocin and related peptides elicit contractions of prostate and seminal vesicle. Ann NY Acad Sci. 1992;652:474-477
11.Litvak J, Borkowski A, Jacobs S, et al. Induction of apop-
tosis by doxazosin: targeting alpha-1 |
blockade |
in benign prostatic hyperplasia. J Urol. |
1997;157: |
1086A |
|
12.Hellstrom W, Schmidt R, Lue T, et al. Neuromuscular dysfunction in nonbacterial prostatitis. Urology. 1987;30(2):183-188
13.Harper G, Barde Y, Burnstock G, et al. Guinea pig prostate is a rich source of nerve growth factor. Nature. 1979;279:160-162
14.Collins A, Robinson E, Neal D. Benign prostatic stromal cells are regulated by basic fibroblast growth factor and transforming growth factor beta 1. J Endocrinol. 1996;151:315-322
15.Paul A, Grant E, Habib F. The expression and localization of beta nerve growth factor in benign and malignant human prostate tissue: relationship to neuroendocrine differentiation. Br J Cancer. 1996;74:1990-1996
16.Story M, Hopp K, Meier D. Regulation of basic fibroblast growth factor expression by transforming growth factor beta in cultured human prostate stromal cells. Prostate. 1996;28:219-226
17.Elbadawi A, Goodman D. Autonomic innervation of accessory male genital glands. In: Spring-Mills E, Hafez E, eds. Male Accessory Sex Glands. Amsterdam: Elsevier- North-Holland Biomedical Press; 1980
18.Gosling J. Autonomic innervation of the prostate. In: Hinman F, ed. Benign Prostatic Hypertrophy. New York: Springer; 1983:349-360:chap 32
19.Higgins J, Gosling J. Studies on the structure and intrinsic innervation of normal human prostate. Prostate. 1989;2:5-16
20.Crowe R, Chapple C, Burnstock G. The human prostate gland: a histochemical and immunohistochemical study of neuropeptides, serotonin, dopamine beta-hydroxylase and acetylcholinesterase in autonomic nerves and ganglia. Br J Urol. 1991;68(1):53-61
21.Dail WG. Autonomic innervation of male reproductive genitalia. In: Maggi CA, ed. The Autonomic Nervous System. Nervous Control of the Urogenital System, vol. 6. London: Harwood Academic Publishers; 1993:69101:chap 9
22.Benoit G, Merlaud L, Meduri G, et al. Anatomy of the prostatic nerves. Surg Radiol Anat. 1994;16(1):23-29
23.Setchell B, Maddocks S, Brooks D. Anatomy, Vasculature Innervation, and Fluids of the Male Reproductive Tract. New York: Raven Press; 1994
24.Vaalasti A. Autonomic innervation of the human male accessory sex glands. In: Riva A, Testa RF, eds.
Ultrastructure of Male Urogenital Glands: Prostate, Seminal Vesicles, Urethral, and Bulbourethral Glands. New York: Kluwer Academic; 1994:187-196
25.Kepper M, Keast J. Immunohistochemical properties and spinal connections of pelvic autonomic neurons that innervate the rat prostate gland. Cell Tissue Res. 1995;281(3):533-542
26.Marson L, Orr R. Identification of rat spinal neurons that innervate the prostate comparison of hypogastric and pelvic inputs using transneuronal tracing with pseudorabies virus. Soc Neurosci. 1996;22:1051 (Abstract)
27.Dixon J, Jen P, Gosling J. A double-label immunohistochemical study of intramural ganglia from the human male urinary bladder neck. J Anat. 1997;190(1): 125-134
28.Hedlund P, Larsson B,Alm P, et al. Nitric oxide synthasecontaining nerves and ganglia in the dog prostate: a comparison with other transmitters. Histochem J. 1996;28(9):635-642
29.Hedlund P, Ekstrom P, Larsson B, et al. Heme oxygenase and NO synthase in the human prostate-relation to adrenergic, cholinergic and peptide containing nerves.
J Autonom Nerv Syst. 1997;63:115-126
30.Gosling J, Thompson S.A neurohistochemical and histological study of peripheral autonomic neurons of the human bladder neck and prostate. Urol Int. 1977;32:269
31.Baumgarten H, Falck B, Holstein A, et al. Adrenergic innervation of the human testis, epididymis, ductus deferens and prostate: a fluorescence microscopic and fluorometric study. Z Fur Zellforsch Und Mikrosk Anat. 1968;90(1):81-95
32.Alm P, Allumets J, Hakanson R, et al. Peptidergic (vasoactive intestinal peptide) nerves in the genitourinary tract. Neuroscience. 1977;2(5):751-754
33.Dunzendorfer U, Jonas D, Weber W. The autonomic innervation of the human prostate. Histochemistry of acetylcholinesterase in the normal and pathologic states. Urol Res. 1976;4:29-32
34.Yokoyama R, Inokuchi T, Satoh H, et al. Distribution of tyrosine hydroxylase (TH)-like, neuropeptide Y (NPY)- like immunoreactive and acetylcholinesterase (ACHE)- positive nerve fibers in the prostate gland of the monkey (Macacus fuscatus). Kurume Med J. 1990;37(1):1-8
35.Danuser H,Springer J,Katofiasc M,et al.Extrinsic innervation of the cat prostate gland; a combined tracing and immunohistochemical study. J Urol. 1997;157(3):1018-1024
36.Dixon J, Jen P, Gosling J. The distribution of vesicular acetylcholine transporter and NPY in and nitric oxide in the human genitourinary organs. Neurourol Urodynam. 2000;19:185-194
247
Physiology and PharMacology of thE ProstatE
37.Vaalasti A, Hervonen A. Autonomic innervation of the human prostate. Invest Urol. 1980;17(4):293-297
38.Shirai M, Sasaki K, Rikimaru A. A histochemical investigation of the distribution of adrenergic and cholinergic nerves in the human male genital organs. Tohoku J Exp Med. 1973;111:281-291
39.Plancarte R, Amescua C, Patt RB, et al. Superior hypogastric plexus block for pelvic cancer pain. Anesthesiology. 1990;73(2):236-239.
40.Lique M, Coolen JA, Truitt WA, McKenna KE. Central regulation of ejaculation. Physiol Behav. 2004;83(2): 203-215
41.Perichino M, Bozzo W, Puppo P, et al. Does transurethral thermotherapy induce long-term alpha blockade? An immunohistochemical study. Eur Urol. 1993;23:299-301
42.Arai Y, Jukuzawa S, Terai A, Yoshida O. Transurethral microwave thermotherapy for benign prostatic hyperplasia – relation between clinical response and prostate histology. Prostate. 1996;28(2):84-88
43.Chuang YC, Chiang PH, Yoshimura N, De Miguel F, Chancellor MB. Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia. BJU Int. 2006;98:1033-1037
44.Vaalasti A,Linnoila I,Hervonen A.Immunohistochemical demonstration of VIP, [Met5]-and [Leu5]-enkephalin immunoreactive nerve fibers in the human prostate and seminal vesicles. Histochemistry. 1980;66:89-98
45.Eckhardt C. Untersuchungen uber die Erection des Penis beim Hunde. Beitr Anat Physiol. 1863;3:123-166
46.Hedlund H, Andersson K, Larsson B. Alphaadrenoceptors and muscarinic receptors in the isolated human prostate. J Urol. 1985;134:1291-1298
47.Lepor H, Shapiro E. Characterization of alpha1-adrener- gic receptors in human benign prostatic hyperplasia. J Urol. 1984;132:1226-1229
48.Hiebel J, Ruffolo R. The use of alpha-adrenoceptor antagonists in the pharmacological management of benign prostatic hypertrophy: an overview. Pharmacol Res. 1996;33(3):145-160
49.Shapiro E, Lepor H. Alpha2 adrenergic receptors in hyperplastic human prostate: identification and characterization using 3 H-rauwolscine. J Urol. 1986;135: 1038-1043
50.Lepor H, Gup DI, Bauman M, et al. Laboratory assessment of terazosin and a1 blockade in prostatic hyperplasia. Urology. 1988;32:21-26
51.Kitada S, Kumazawa J. Pharmacological characteristics of smooth muscle in benign prostatic hyperplasia and normal prostatic tissue. J Urol. 1987;138:158-160
52.Chapple CR, Aubrey ML, James S, et al. Characterisation of human prostatic adrenoceptors using pharmacology receptor binding and localization. Br J Urol. 1989;63: 487-496
53.Gup D, Shapiro E, Buamann M, et al. Contractile properties of human prostate adenomas and the development of infravesical obstruction. Prostate. 1989;15:105-114
54.Eri L, Tveter KJ. a-Blockade in the treatment of symptomatic benign prostatic hyperplasia. J Urol. 1995;154: 923-934
55.Andersson KE, Lepor H,Wyllie M. Prostate a1 adrenoceptor and uroselectivity. Prostate. 1977;30:202-216
56.Chapple CR. Selective a1-adrenoceptor antagonists in benign prostatic hyperplasia: rationale and clinical experience. Eur Urol. 1996;129:144
57.Jardin A, Andersson K-E, Caine M, et al. a-blockers therapy in benign prostatic hyperplasia. In: Cockett ATK, Khoury S, Aso Y, Chatelain C, Denis L, Griffiths K, Murphy C, eds. The Third International Consultation on Benign Prostatic Hyperplasia (BPH). New York: SCI; 1996:527-564
58.Forray C, Bard JA, Wetzel JM, et al. The a1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human a1c subtype. Mol Pharmacol. 1994;45:703-708
59.Marshall I, Burt RP, Chapple CR. Noradrenaline contractions of human prostate mediated by a1a-(a1c-)adreno- ceptor subtype. Br J Pharmacol. 1995;115:781-786
60.Fabiani ME, Sourial M, Thomas WG, et al. Angiotensin II enhances noradrenaline release from sympathetic nerves of the rat prostate via a novel angiotensin receptor: implications for the pathophysiology of benign prostatic hyperplasia. J Endocrinol. 2001;171(1): 97-108
61.Caine M, Raz S, Zeigler M. Adrenergic and cholinergic receptors in the human prostate, prostatic capsule and bladder neck. Br J Urol. 1975;47:193-202
62.Appell RA, England HR, Hussell AR, et al. The effect of epidural anesthesia on the urethral closure pressure profile in patients with prostatic enlargement. J Urol. 1980;124:410-411
63.Furuya S, Kumamoto Y, Yokoyama E, et al. Alphaadrenergic activity and urethral pressure in prostatic zone in benign prostatic hypertrophy. J Urol. 1982;128:836-839
64.Nickel JC. Alpha-blockers for the treatment of prostati- tis-Like syndromes. Rev Urol. 2006;8(suppl 4):S26-S34
65.Farrell J, Lyman Y. A study of the secretory nerves and the action of certain drugs on, the prostate gland. Am J Phys. 1937;118:64-70
66.Smith E, Lebeaux M. The mediation of the canine prostatic secretion provoked by hypogastric nerve stimulation. Invest Urol. 1970;7(4):313-318
67.Smith E, Lebeaux M. The composition of nerve induced canine prostatic secretion.Invest Urol.1971;8(2):100-103
68.Bruschini H, Schmidt R, Tanagho E. Neurologic control of prostatic secretion in the dog. Invest Urol. 1978; 15(4):288-290
69.Smith ER. The canine prostate and its secretion. In: Thomas JA, Singhai R, eds. Molecular Mechanisms of Gonadal Hormone Action. Baltimore, MD: University Park Press; 1975:167-204
70.Wang J, McKenna KE, Lee C. Determination of prostatic secretion in rats: effect of neurotransmitters and testosterone. Prostate. 1991;18:289-301.
71.Lepor H, Khuhar M. Characterization of muscarinic cholinergic receptor binding in the vas deferens, bladder, prostate and penis of the rabbit. J Urol. 1984;132: 392-396
72.James S, Chapple C, Phillips M, et al. Autoradiographic analysis of alpha-adrenoceptors and muscarinic cholin-
ergic receptors in the hyperplastic human prostate. J Urol. 1989;142(2 Pt 1):438-444
248
Practical Urology: EssEntial PrinciPlEs and PracticE
73.Burnett A, Takeda M, Maguire M, et al. Characterization and localization of nitric oxide synthase in the human prostate. Urology. 1995;45:435-439
74.Jen P, Dixon J, Gosling J. Co-localisation of tyrosine hydroxylase, nitric oxide synthase and neuropeptides in neurons of the human postnatal male pelvic ganglia. J Autonom Nerv Syst. 1996;59(1–2):41-50
75.Jen P, Dixon J, Gerahart J, et al. Nitric oxide synthase and tyrosine hydroxylase are co-localized in nerves supplying the postnatal human male genitourinary organs. J Urol. 1996;155(3):1171-1121
76.Jen P, Dixon J. Development of peptide-containing nerves in the human fetal prostate gland. J Anat. 1995; 187(Pt. 1):169-179
77.Takeda M, Tang R, Shapiro E, et al. Effects of nitric oxide on human and canine prostates. Urology. 1995;45:440-446
78.Isaacs J, Steinberg G. A guide to the physiology of the prostate. Cont Urol. 1990;47:54-66
79.McVary KT, Monnig W, Camps JL Jr, Young JM, Tseng LJ, van den Ende G. Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized,double-blind trial. J Urol. 2007;177:1071-1077
80.McVary KT, Roehrborn CG, Kaminetsky JC, et al. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol. 2007;177: 1401-1407
81.Stief CG, Porst H, Neuser D, Beneke M, Ulbrich E. A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur Urol. 2008;53:1236-1244
82.Smith E, Miller T, Pebler R. Transepithelial voltage changes during prostatic secretion in the dog. Am Phys Soc. 1983;245:F470-F477
83.Jacobs SC, Story MT. Autonomic control of acid phosphatase exocrine secretion by the rat prostate. Urol Res. 1989;17:311-315
84.Martinez-Pineiro L, Dahiya R, Nunes L, et al. Pelvic plexus denervation in rats causes morphologic and functional changes of the prostate. J Urol. 1993;150(1): 215-218
85.Wang J, McKenna K, McVary K, et al. Requirement of innervation for maintenance of structural and functional integrity in the rat prostate. Biol Reprod. 1991;44(6):1171-1176
86.McVary KT, Razzaq A, Lee C, et al. Growth of the rat prostate gland is facilitated by the autonomous nervous system. Biol Reprod. 1994;51:99-107
87.Vaalast A, Alho AM, Tainio H. The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem. 1986;79:49-54
88.Lamano-Carvalho TL, Favaretto AL, Petenusci SO, et al. Prepubertal development of rat prostate and seminal vesicle following chemical sympathectomy with guanethidine. Braz J Med Biol Res. 1993;26(6): 639-646
89.Huang HFS, Li MT, Linsenmeyer T, et al. The effects of spinal cord injury on the status of messenger ribonucleic acid for TRPM2 and androgen receptor in the prostate of the rat. J Androl. 1997;18:250-256
90.Djavan B, Marberger M. A meta-analysis on the effi-
cacy and tolerability of a1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol. 1999;36:1-13
91.de Reijke TM, Klarskov P. Comparative efficacy of two a-adrenoreceptor antagonists,doxazosin and alfuzosin, in patients with lower urinary tract symptoms from benign prostatic enlargement. BJU Int. 2004;93:757-762
92.Hellstrom WJ, Sikka SC. Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers. J Urol. 2006;176:1529-1533
93.Foley SJ, Soloman LZ, Wedderburn AW, et al. A prospective study of the natural history of hematuria associated with benign prostatic hyperplasia and the effect of finasteride. J Urol. 2000;163:496-498
94.Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215-224
95.Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. N Engl J Med. 1992;327:1185-1191
96.Roehrborn CG,Marks LS,Fenter T,et al.Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia.Urology. 2004;63:709-715
97.Roehrborn CG. Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study. BJU Int. 2006;97:734-741
98.Kirby RS, Roehrborn C, Boyle P, et al. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology. 2003;61:119-126
99.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
100.McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin,finasteride,and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387-2398