Pharmacologic targets on the female urethra.
BACKGROUND
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.


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
alpha-Adrenoceptors (ARs) cause contraction and beta-ARs cause relaxation. Use of selective alpha-agonist and beta-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.
Canda
A Erdem
AE
Manisa State Hospital, Urology Clinic, Manisa, Turkey. aecanda@yahoo.com
Cinar
Mehtap G
MG
Turna
Burak
B
Sahin
M Oguz
MO
D000322:Adrenergic Agonists / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006801:Humans; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014521:Urethra / Q000187:drug effects* / Q000294:innervation; D014549:Urinary Incontinence / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D014550:Urinary Incontinence, Stress / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
D000322:Adrenergic Agonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D017981:Receptors, Neurotransmitter