title: Up-regulation of α1a and α1d-adrenoceptors in the prostate by administration of subtype selective α1-adrenoceptor antagonist tamsulosin in patients with benign prostatic hyperplasia.
abstract: OBJECTIVE
  We examined the change in α(1)-adrenoceptor subtype expression in the prostate due to chronic tamsulosin administration in a benign prostatic hyperplasia rat model and in patients.
  
  
  METHODS
  We measured α(1)-adrenoceptor subtype expression after tamsulosin administration in the prostate of the benign prostatic hyperplasia rat model using TaqMan® reverse transcriptase-polymerase chain reaction. We also measured expression before and after 12-week tamsulosin treatment in the prostate of patients with benign prostatic hyperplasia. We examined the correlation between the change in α(1)-adrenoceptor expression due to tamsulosin treatment and acute urinary retention during long-term followup.
  
  
  RESULTS
  The expression of α(1a) and α(1d)-adrenoceptors was significantly increased in dose dependent fashion by tamsulosin in the benign prostatic hyperplasia rat model. Median mRNA expression of subtypes α(1a) and α(1d)-adrenoceptors was 1.4 (IQR 0.6, 3.0) and 1.7 × 1,000 copies per 1 ng β-actin (IQR 0.9, 2.4) before treatment, and 6.0 (IQR 2.0, 8.0) and 2.2 × 1,000 copies per 1 ng β-actin (IQR 1.7, 3.6), respectively, after treatment. The expression of α(1a) and α(1d)-adrenoceptors significantly increased after tamsulosin treatment (p <0.01 and <0.05, respectively). This increase was observed in 10 patients in whom acute urinary retention did not develop during long-term followup but not in 4 in whom acute urinary tract retention developed.
  
  
  CONCLUSIONS
  Tamsulosin up-regulated α(1a) and α(1d)-adrenoceptors, suggesting that it has clinical selectivity for α(1a) and α(1d)-adrenoceptors. Up-regulation of α(1)-adrenoceptors subtype expression is considered an adaptive response to chronic tamsulosin administration. The difference in the response to α(1)-adrenoceptors antagonists among patients may contribute to the diversity in the long-term efficiency of α(1)-adrenoceptor antagonists.
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. ykojima@med.nagoya-cu.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kojima
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kubota
authors.forename: Makoto
authors.initials: M
authors.lastname: Imura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oda
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kiniwa
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013449:Sulfonamides / Q000627:therapeutic use*; D000077409:Tamsulosin; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D000077409:Tamsulosin