Change of expression levels of alpha1-adrenoceptor subtypes by administration of alpha1d-adrenoceptor-subtype-selective antagonist naftopidil in benign prostate hyperplasia patients.
BACKGROUND
We examined whether the change of alpha(1)-adrenoceptor (alpha(1)-AR) subtype expression levels in the prostate occurred by administration of the alpha(1d)-AR-subtype-selective antagonist naftopidil to benign prostate hyperplasia (BPH) patients, and discussed the possible alternation of its effectiveness by the chronic administration of alpha(1)-AR antagonists.


METHODS
Fifteen patients with untreated BPH aged 58-76 (mean age, 68.2 +/- 7.4 years) underwent prostate biopsy from the transition zone before and after 50 mg naftopidil administration daily for 12 weeks. Taqman quantitative reverse transcription polymerase chain reaction was performed using these biopsy specimens to estimate the expression level of each alpha(1)-AR subtype. Comparison was made of the expression level of alpha(1)-AR subtypes before and after naftopidil administration. We also examined the correlation between the change of alpha(1)-AR subtype expression levels and the short-term efficacy of naftopidil.


RESULTS
Naftopidil administration for 12 weeks down-regulated the expression of alpha(1a)-AR and alpha(1b)-AR mRNA and up-regulated the expression of alpha(1d)-AR mRNA without a change in the total alpha(1)-AR mRNA expression level. There was no correlation between the change of alpha(1)-AR subtype expression levels and the short-term efficacy of naftopidil for BPH patients.


CONCLUSIONS
The change of alpha(1d)-AR expression level may be regarded as a compensatory adaptation to chronic alpha(1d)-AR antagonist naftopidil administration. This may mean that long-term use of the same alpha(1)-AR antagonist for BPH patients induces therapeutic tolerance.
Kojima
Yoshiyuki
Y
Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. ykojima@med.nagoya-cu.ac.jp
Sasaki
Shoichi
S
Shinoura
Hitomi
H
Hayase
Masa
M
Kubota
Yasue
Y
Hayashi
Yutaro
Y
Tsujimoto
Gozoh
G
Kohri
Kenjiro
K
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000368:Aged; D001706:Biopsy; D015153:Blotting, Western; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D010879:Piperazines; D020033:Protein Isoforms; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; C064357:naftopidil