A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders.
OBJECTIVE
We compared the expression level of alpha 1-adrenoceptor (AR) subtype mRNA to that of beta-AR subtype mRNA in control and obstructed human bladders, and examined whether alpha 1-AR mediated contraction and beta-AR mediated relaxation of human detrusor muscle are altered by bladder outlet obstruction.


METHODS
A real-time quantitative reverse transcriptase-polymerase chain reaction based method was used to quantify alpha1 and beta-AR subtype mRNA expression. The contractile response to alpha-AR agonists and the relaxant effect of beta-AR agonists were examined using an isometric contraction technique.


RESULTS
The mRNA of alpha 1a, alpha 1b, alpha 1d, beta 1 and beta 2-AR mRNAs was expressed at low levels, while beta 3-AR was the most highly expressed subtype at the mRNA level in control and obstructed bladders. The expression level of alpha 1 and beta-AR subtype mRNA was not significantly different between the 2 groups. The mean contractile response to 10(-4) M phenylephrine +/- SEM was only 4.4% +/- 1.4% and 5.2% +/- 1.4% of the 10(-7) M carbachol induced contraction in the control and obstructed groups, respectively. Contractile responses to phenylephrine were not significantly increased in obstructed bladder. Isoproterenol and the beta 3-AR selective agonist L755,507 relaxed human detrusor muscle in a concentration dependent manner (10(-9) to 10(-4) M). However, the beta 1/beta 2-AR agonist dobutamine and the beta 2-AR selective agonist clenbuterol did not produce relaxation at a concentration of 10(-9) to 10(-5) M in the 2 groups.


CONCLUSIONS
These findings indicate that neither up-regulation of alpha1-ARs nor down-regulation of beta-ARs occurs and relaxation mediating beta 3-ARs are by far predominant in the human obstructed bladder. Therefore, it is not likely that bladder alpha1-ARs are responsible for detrusor overactivity and storage symptoms in patients with benign prostatic obstruction.
Nomiya
Masanori
M
Department of Urology, Fukushima Medical University School of Medicine, Fukushima City, Japan.
Yamaguchi
Osamu
O
D000322:Adrenergic Agonists / Q000494:pharmacology; D000368:Aged; D002217:Carbachol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001743:Urinary Bladder / Q000378:metabolism / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism* / Q000503:physiopathology
D000322:Adrenergic Agonists; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D002217:Carbachol