title: Pharmacologic characterization of human male urethral smooth muscle: an in vitro approach.
abstract: OBJECTIVE
  To elucidate the functional responses of isolated human urethral smooth muscle to various agents known to exert smooth muscle contraction or relaxation.
  
  
  METHODS
  Specimens of penile urethra were obtained from male patients who had undergone male-to-female gender reassignment surgery. Using the tissue bath technique, the contraction induced by increasing concentrations (1 nM-10 μM) of norepinephrine, phenylephrine, acetylcholine, carbachol, prostaglandin F2α, endothelin 1, angiotensin II, and oxytocin was measured. In another set-up, the effects of C-type natriuretic peptide (0.1 nM-1 μM), sodium nitroprusside, sildenafil, forskolin, alpha2-antagonist delquamine, and acetylcholine (1 nM/10 nM-10 μM) on the tension induced by norepinephrine were investigated. The production of cyclic guanosine monophosphate (GMP) and cyclic adenosine monophosphate (AMP) was measured by means of specific radioimmunoassays.
  
  
  RESULTS
  Endothelin 1, oxytocin, prostaglandin F2α, norepinephrine, and phenylephrine induced dose-dependent contraction of the isolated urethral tissue, whereas acetylcholine, carbachol, and angiotensin II had no or only minor contractile effects. The contraction induced by norepinephrine was reversed by the drugs with the following rank order of efficacy: sodium nitroprusside > delquamine > sildenafil > C-type natriuretic peptide > forskolin > acetylcholine. The maximal reversion of tension ranged from 68% (sodium nitroprusside) to 22% (acetylcholine). The relaxing effects of the drugs were paralleled by a several-fold increase in tissue levels of cyclic GMP and cyclic adenosine monophosphate.
  
  
  CONCLUSIONS
  The results provide evidence that urethral smooth muscle is under the control of endogenous compounds, such as adrenergic agonists (norepinephrine and phenylephrine), vasoactive peptides, prostagladins, NO/cyclic GMP, and acetylcholine, assumed to influence micturition at the peripheral level.
authors.affiliation: Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany. Electronic address: kedia.george@mh-hannover.de.
authors.forename: George T
authors.initials: GT
authors.lastname: Kedia
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelke
authors.forename: Michael
authors.initials: M
authors.lastname: Sohn
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Stefan
authors.initials: S
authors.lastname: Ückert
mesh_terms: D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D015237:Dinoprost / Q000494:pharmacology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D010120:Oxytocics / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D014521:Urethra
chemical_list: D019332:Endothelin-1; D010120:Oxytocics; D010656:Phenylephrine; D010121:Oxytocin; D015237:Dinoprost; D000242:Cyclic AMP; D006152:Cyclic GMP; D009638:Norepinephrine