title: Characterization of α1-adrenoceptor subtypes mediating contraction in human isolated ureters.
abstract: OBJECTIVE
  To characterize the contractile functions of the α(1)-adrenoceptor (AR) subtypes present in the human ureter.
  
  
  METHODS
  Specimens were taken from patients with renal cancer ("upper ureters;" n = 51) or bladder cancer ("lower ureters;" n = 23) who had not been treated by chemotherapy, radiation therapy, or immunotherapy before surgery. Patients systemically taking an α(1)-AR agonist or antagonist were excluded from this study. The effects of α(1)-AR antagonists against phenylephrine (α(1)-AR agonist)-induced contractions were evaluated in human isolated ureteral preparations.
  
  
  RESULTS
  Pooled data from all ureters showed that phenylephrine (α(1)-AR agonist) induced a concentration-dependent tonic contraction (pD(2) value, 4.92 ± 011). The phenylephrine-induced maximum contraction was significantly greater in lower ureters than in upper ones. Prazosin (nonselective α(1)-AR antagonist), silodosin (selective α(1A)-AR antagonist), and BMY-7378 (selective α(1D)-AR antagonist) all shifted the concentration-contractile response curve for phenylephrine to the right, the rank order of potencies in all ureters (pK(B) values) being silodosin (9.72 ± 0.14) > prazosin (8.64 ± 0.08) > BMY-7378 (7.04 ± 0.14). The α(1A)-AR antagonist silodosin was thus much more potent than the other 2 antagonists.
  
  
  CONCLUSIONS
  Our results suggest that among α(1)-ARs, the α(1A) subtype plays the major role in contraction in the human ureter.
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan. ssk@med.nagoya-cu.ac.jp
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Shinya
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kojima
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kubota
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014513:Ureter / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C095285:silodosin; C053428:BMY 7378; D011224:Prazosin