Pharmacologic Targets on the Female Urethra

Abstract

Introduction: This article reviews the mechanisms affecting contraction and relaxation of the urethra in order to establish a basis for current and future treatments for urinary incontinence in women. Material and Methods: A review of the English literature using MEDLINE was performed between 1970 and 2008 on female urethra pharmacology, urinary incontinence, and mechanisms involved in contraction and relaxation of the female human urethra. Results: α-Adrenoceptors (ARs) cause contraction and β-ARs cause relaxation. Use of selective α-agonist and β-AR blocker agents might have potential for the treatment of stress urinary incontinence. Tolerable doses of cholinergic agonists did not have significant effects on intraurethral pressure. Nitric oxide seems to be the major nonadrenergic-noncholinergic inhibitory transmitter causing relaxation. c-kit-positive interstitial cells seem to regulate urethral tone. The roles of adenosine triphosphate and carbon monoxide have not been fully investigated in humans. Neuropeptides function similarly to the urinary bladder. Prostanoids cause urethral contraction and relaxation depending on their subtypes. Serotonin enhances the strength of urethral sphincteric contractions. The Rho-kinase pathway also appears to be modulating smooth muscle contraction in the urethra. Conclusions: Understanding of the urethral function and pharmacology may lead to the development of promising new agents which might be useful in the management of urinary incontinence in women.

Does diabetes affect the intensity of staining of interstitial cells and neuronal tissue in the bladder, prostate and urethra of rabbits?

“…Another area for research may be the evaluation of the effects of diabetes on the urinary tract by organ bath experiments with the same tissue (diabetes and controls) as we used for our immunochemical investigations. It is known that organ bath experiments are the gold standard for functional evaluation of contractile tissue such as that in the urinary tract [22][23][24]. The urinary bladder and urethra are innervated by cholinergic (parasympathic), adrenergic (sympathic), and non-adrenergic noncholinergic pathways (NANC) [23,24].…”

“…It is known that organ bath experiments are the gold standard for functional evaluation of contractile tissue such as that in the urinary tract [22][23][24]. The urinary bladder and urethra are innervated by cholinergic (parasympathic), adrenergic (sympathic), and non-adrenergic noncholinergic pathways (NANC) [23,24]. Therefore, it would be interesting to know to what extent diabetes affects the contractile responses in these tissues through the intensity of staining of neural tissue and ICs, as we demonstrated in our study.…”

Ion channels of the mammalian urethra

“…[8][9][10][11] The adult female urethra is embedded in the anterior vaginal wall and typically ranges 3-4 cm in length and »0.6 cm in luminal diameter. 12,13 Although the male urethra is »20 cm in length, it is mainly the prostatic and pre-prostatic regions ( Fig. 1) that contribute to the true internal urethral sphincter.…”

“…During the urine filling/storage phase, urine outflow from the bladder does not occur by virtue of the fact that the bladder musculature is largely relaxed and electrically quiescent, while the urethra, a conduit muscular tube extending from the base of the bladder, maintains a constant tone and is effectively closed (excellent reviews are available describing bladder and urethral physiology/pharmacology). 6,13 Early studies utilizing catheters in humans reported a time-delay ranging from 5-15 seconds between the relaxation of urethral musculature and contraction of the bladder detrusor muscle. [15][16][17][18] It is well-established that the inability of the urethral musculature to maintain sufficient tone can result in involuntary urine leakage.…”

Een α‑adrenerge receptorantagonist als behandeling van blaasontledigingsklachten bij vrouwen: Feit of fictie?

“…Verscheidene studies hebben aangetoond dat ook de vrouwelijke urethra α1-receptoren bevat [2][3][4]. Uit invitro-onderzoeken bij vrouwtjeskonijnen blijkt dat er middels stimulatie van deze α1-receptoren door noradrenalinereceptorantagonist in de urethra een rustspanning wordt gewaarborgd.…”