Doxazosin-induced up-regulation of alpha 1A-adrenoceptor mRNA in the rat lower urinary tract.
Alpha1-adrenoceptor (AR) antagonists can provide effective treatment of symptoms caused by benign prostatic hyperplasia. However, their mechanisms of action have not been fully elucidated. We previously reported that chronic administration of doxazosin causes an up-regulation in the mRNA expression of all three alpha1-AR subtypes in the rat prostate. As alpha1-AR antagonists might also affect the properties of alpha1-ARs in the lower urinary tract, we examined the effects of doxazosin (2 or 4 mg/kg daily subcutaneously, supplemented with 4 mg/kg daily orally for 8 or 12 weeks) on alpha1-AR subtype mRNAs in the rat bladder dome, bladder base, and urethra using real-time reverse transcription PCR. Rats that received the highest doses of doxazosin had significantly heavier bladder base and prostatic urethra than controls. PCR data showed that all three alpha1-AR subtypes were expressed in all tissues studied. Doxazosin treatment caused an up-regulation in the mRNA levels of alpha1A-AR in the rat bladder base and prostatic urethra, indicating that chronic doxazosin treatment may cause an alteration in the properties of alpha1A-AR subtype mRNA in these two areas. Furthermore, the heavier bladder base and prostatic urethra in the doxazosin-treated rats suggest that alpha1-AR antagonist treatment might also influence the growth process in these areas of the rat lower urinary tract.
Yono
Makoto
M
Section of Urology, Yale University School of Medicine, New Haven, CT 06520, USA.
Foster
Harris E
HE
Shin
David
D
Takahashi
Wataru
W
Pouresmail
Mehdi
M
Latifpour
Jamshid
J
D000818:Animals; D017292:Doxazosin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis* / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D014551:Urinary Tract / Q000187:drug effects* / Q000378:metabolism
C547715:Adra1a protein, rat; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D017292:Doxazosin