Investigations into the Presence of Functional
E
1,
E
2 and
E
3-Adrenoceptors in Urothelium and Detrusor of Human Bladder
Pradeep Tyagi, Catherine A. Thomas, Naoki Yoshimura, Michael B. Chancellor
Department of Urology (CAT, NY, PT), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA, and Department of Urology (MBC), William Beaumont Hospital, Royal Oak, Michigan, USA
ABSTRACT
Purpose:We investigated the presence of functional E1,E2 and E3-adrenoceptor in urothelium and detrusor muscle of KXPDQEODGGHUWKURXJKLQYLWURSKDUPDFRORJ\RIVHOHFWLYHȕDGUHQRFHSWRUDJRQLVWVRODEHJURQ
Materials and Methods: Expression of these adrenoceptors in surgically separated human urothelium and detrusor muscle ZHUH LQYHVWLJDWHG XVLQJ 573&5 7KH HIIHFWV RI DFWLYDWLQJ WKHVH UHFHSWRUV ZHUH VWXGLHG E\ GHWHUPLQLQJ WKH UHOD[DWLRQHUH LQYHVWLJDWHG XVLQJ 573&5 7KH HIIHFWV RI DFWLYDWLQJ WKHVH UHFHSWRUV ZHUH VWXGLHG E\ GHWHUPLQLQJ WKH UHOD[DWLRQLQYHVWLJDWHGXVLQJ573&57KHHIIHFWVRIDFWLYDWLQJWKHVHUHFHSWRUVZHUHVWXGLHGE\GHWHUPLQLQJWKHUHOD[DWLRQ produced by EDGUHQRFHSWRUVDJRQLVWLQSUHFRQWUDFWHGKXPDQGHWUXVRUVWULSV
Results:7KHUHVXOWVFRQ¿UPHGWKHSUHVHQFHRIP51$IRUE1, E2 and E3-adrenoceptor in both human urothelium and GHWUXVRU,QDQLQYLWURIXQFWLRQDOEODGGHUDVVD\6RODEHJURQDQGRWKHUDJRQLVWVIRUE-adrenoceptors such as procaterol and isoproterenol evoked potent concentration-dependent relaxation of isolated human bladder strips with pD2YDOXHVRI
rrDQGrUHVSHFWLYHO\
Conclusions:6HOHFWLYHEDGUHQRFHSWRUDJRQLVWPD\EHDSRWHQWLDOQHZWUHDWPHQWIRUWKHRYHUDFWLYHEODGGHU2$%V\Q -GURPH([LVWHQFHRIEDGUHQRFHSWRUP51$H[LVWVLQWKHXURWKHOLXPLQDGGLWLRQWRWKHGHWUXVRUPXVFOHVXJJHVWPXOWLSOH site of actions for the EDGUHQRFHSWRULQWKHORZHUXULQDU\WUDFW
Key words: bladder; urothelium; detrusor; adrenoreceptors Int Braz J Urol. 2009; 35: 76-83
INTRODUCTION
7KH RYHUDFWLYH EODGGHU 2$% V\QGURPH DIIHFWVPRUHWKDQPLOOLRQSHRSOHLQWKH8QLWHG 6WDWHV0XVFDULQLFUHFHSWRUDQWDJRQLVWVDUHWKHPRVW
common form of pharmacologic treatment therapy
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mechanistic side effects related to effect of these
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evoked bladder contraction and alternative approach may be to develop drugs acting on the storage phase
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the muscarinic receptor antagonists act during the
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that bladder relaxation mediated by E-adrenoceptors will be a viable target, because increased relaxation of the detrusor smooth muscle will lengthen the dura-tion of storage phase in micturidura-tion cycle and thereby
DOOHYLDWHWKHV\PSWRPVRI2$%
6WXGLHVKDYHVKRZQWKDWEODGGHUUHOD[DWLRQ
evoked by E-adrenoceptor agonists is mainly medi-ated by EDGUHQRFHSWRULQPRVWVSHFLHV E3-ad-renoceptor agonist are said to stimulate the G protein
-nophosphate and causes relaxation of smooth muscle
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E-adrenoreceptor induced relaxation of bladder are
DOVRQRWUXOHGRXW6WXGLHVKDYHVKRZQWKDWDWOHDVW RIWKHDGUHQRFHSWRUWUDQVFULSWVLQKXPDQEODG -der are represented by EDGUHQRFHSWRUVXEW\SH 6HOHFWLYHE3-adrenoceptor agonists have been shown
WRFDXVHVLJQL¿FDQWUHOD[DWLRQRIKXPDQEODGGHUVWULSV
as compared with E1 and E2-adrenoceptor agonists,, and this was observed in normal and neurogenic blad-this was observed in normal and neurogenic
blad-GHUVE3-adrenoceptor agonists are expected to be
FOLQLFDOO\XVHIXODJHQWVLQWKHWUHDWPHQWRIWKH2$% V\QGURPH
$OWKRXJK H[SUHVVLRQ RIE-adrenoceptors in human bladder has been previously reported us-ing receptor-bindus-ing studies, but the anatomical
GLVWULEXWLRQRIWKHH[SUHVVLRQDQG ZKLFK VXEW\SHVDQGZKLFK VXEW\SHVZKLFKVXEW\SHV
of E-adrenoceptor are expressed in the urothelium hasare expressed in the urothelium has
RQO\UHFHQWO\EHHQLQGLFDWHG([SUHVVLRQ RIExpression of of E-ad-renoceptors in urothelium is favored by the mounting evidence in support of a important role played by bladder epithelial cells in modulating bladder activity in response to local chemical and mechanical stimuli
7KXVLQ WKLV VWXG\ ZH DLPHG WR LQYHVWLJDWH WKHn this study, we aimed to investigate thewe aimed to investigate theto investigate the presence of E1-,E2- and E3-adrenoceptor in separate tissue of urothelium and detrusor muscle from human
EODGGHU)XQFWLRQDOVLJQL¿FDQFHRIE3-adrenoceptors
ZDVLQYHVWLJDWHGE\VWXG\LQJWKHHIIHFWVRI*:*: RU6RODEHJURQ6RODEHJURQ, a selective a selective E3-adrenoceptor agonist
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MATERIALS AND METHODS
Human bladders - The human bladders were
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informed consent from the next of kin of the six organ donors using an honest broker system from the Health
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disease status of organ donors was not available to
WKHVWXG\LQYHVWLJDWRUV
,VRODWHGEODGGHUVWULSV7KHPXFRVDDQGDG -ventitia was removed and longitudinal detrusor strips
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sutures were tied to each end of the strips, and tissues
were lowered into the myobath multi-channel tissue
EDWKV\VWHP:RUOG3UHFLVLRQ,QVWUXPHQWV6DUDVRWD )ORULGD86$7KHFKDQJHVLQPXVFOHWHQVLRQZHUH GLJLWDOO\ UHFRUGHG E\ 3RZHU/DE 6RIWZDUH &KDUWV $',QVWUXPHQWV &RORUDGR 6SULQJV &2 86$ (DFKWLVVXHVDPSOHZDVVXVSHQGHGLQDP/RUJDQ EDWKFRQWDLQLQJR[\JHQDWHG.UHEVVROXWLRQ1D&O PPROO.&OPPROO1D+&2PPROO .+32PPROO&D&OPPROO0J62 PPROO JOXFRVH PPROO S+ DHUDWHG ZLWK2&22DQGPDLQWDLQHGDW&DQG FRQVWDQWO\DHUDWHGZLWKR[\JHQDQGFDUERQ GLR[LGH7KHWLVVXHVZHUHVXEMHFWHGWRDUHVWLQJWHQ
-VLRQRIJUDPVDQGDOORZHGWRHTXLOLEUDWHIRU PLQGXULQJWKLVWLPHWKHWLVVXHZDVZDVKHGHYHU\ PLQDQGUHVWLQJWHQVLRQZDVDGMXVWHG$IWHUREWDLQLQJ
basal tension of 1-2 grams, muscle contractions were
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E3-DGUHQRFHSWRUDJRQLVWSULRUWRWHVWLQJ()6UHVSRQVHV DQGZLWKDPLQZDVKDIWHUHDFKVWLPXOXV
Chemicals - KCl, procaterol, isoproternol and papaverine were obtained from Tocris bioscience
&DWDORJ(OOLVYLOOH0LVVRXUL86$*:RU
solabegron (a selective EDGUHQRFHSWRU DJRQLVW ZDVSURYLGHGE\*OD[R6PLWK.OLQH3KDUPDFHXWLFDO &RPSDQ\.LQJRI3UXVVLD3$86$$OOVROXWLRQV ZHUHIUHVKO\SUHSDUHGGDLO\'UXJVZHUHGLVVROYHG LQGHLRQL]HGGLVWLOOHGZDWHU)XUWKHUGLOXWLRQVZHUH FDUULHGRXWLQ.UHEVVROXWLRQ7KHFRQFHQWUDWLRQVDUH H[SUHVVHGDVWKH¿QDOPRODUFRQFHQWUDWLRQLQWKHWLVVXH FKDPEHU
573&5VWXGLHV 7RWDO 51$ H[WUDFWLRQ ZDVWXGLHV7RWDO51$H[WUDFWLRQZDV SHUIRUPHGZLWK75,]ROUHDJHQWXVLQJPDQXIDFWXUHU LQVWUXFWLRQV,QYLWURJHQIURPVXUJLFDOO\VHSDUDWHG XURWKHOLXPDQGGHWUXVRUWLVVXHV5HYHUVHWUDQVFULS
-WLRQZLWKJRI51$ZDVIROORZHGE\3&5ZLWK SULPHUVVSHFL¿FIRUWKHF'1$FRGLQJIRUKXPDQ DQGUHFHSWRUVXEW\SHV7DEOH5HDFWLRQV
were performed under certain conditions,
includ-LQJq&IRUPLQXWHVF\FOHVDWqC for 30
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Good separation of the bladder layers was evaluated
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-OLXPDQGGHWUXVRUZHUHVQDSIUR]HQLQOLTXLGQLWURJHQ
immediately after dissection and embedded in OCT
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6WDWLVWLFDOHYDOXDWLRQ5HVXOWVDUHH[SUHVVHG
as means r6(0RIPHDVXUHPHQWVLQVWULSVREWDLQHG IURPDWOHDVWGLIIHUHQWKXPDQEODGGHUVDQGDPD[L
-PXPRIWKUHHVWULSVSHUEODGGHUZHUHXVHG&RQWUDF
-WLOHUHVSRQVHVDUHH[SUHVVHGDVDEVROXWHYDOXHV0
or as percentage of the relaxation induced by 10-3 0SDSDYHULQH&RQFHQWUDWLRQUHVSRQVHGDWDRI.&O ZHUHHYDOXDWHGE\VLJPRLGFXUYH¿WWLQJDQGORJ(&
values (pD2ZHUHFDOFXODWHGE\QRQOLQHDUUHJUHVVLRQ
DQDO\VLVXVLQJ*UDSK3DG3ULVP'LIIHUHQFHVEHWZHHQ PHDQYDOXHVZHUHVWDWLVWLFDOO\DQDO\]HGXVLQJDQXQ
-SDLUHGVWXGHQWWWHVW$SUREDELOLW\YDOXHRIS ZDV UHJDUGHG WR EH VLJQL¿FDQW$OO DQDO\VHV ZHUH
performed using GraphPad Prism software (version
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RESULTS
3UHVHQFH RI WUDQVFULSWV IRU DQG DGUHQRFHSWRUVZDVGHWHUPLQHGE\3&5DPSOL¿
-FDWLRQRIF'1$REWDLQHGIURPVXUJLFDOO\VHSDUDWHG GHWUXVRU DQG XURWKHOLXP WLVVXH RI KXPDQ EODGGHU 6SHFL¿FSULPHUVIRUWKHDQGDGUHQRFHS -tor gene produced a single PCR product of expected
VL]HLQDOOVHWVZKHQVHSDUDWHGRQHWKLGLXPEURPLGH VWDLQHGDJDURVHJHOV)LJXUH6HSDUDWLRQRI
urothelium and detrusor was demonstrated by lack of any smooth muscle tissue stain in H&E staining
)LJXUH7KHODFN RI FRQWDPLQDWLRQ IURP GHWUXVRUlack of contamination from detrusor
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by lack of immunoreactivity for nonvascular smoothnonvascular smooth
PXVFOHVSHFL¿FSURWHLQGHVPLQ LQ XURWKHOLXP GDWDdesmin in urothelium (data
QRWVKRZQ7KHGHWUXVRUWLVVXHVKRZHGVWURQJVWDLQ IRUGHVPLQFRPSDUHGWRDIDLQWVWDLQLQXURWKHOLXP )XQFWLRQDO VLJQL¿FDQFH RI WKHVH UHFHSWRUV
was tested by relaxation of human bladder strips by
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drugs were expressed as a percentage of the 10-30
papaverine induced relaxation of tension produced Table 1 – Primer sequences.
Primer Sequence PCR Product
E1 )RUZDUG7&*7*7*&$&&*7*7***&&
5HYHUVH$**$$$&**&*&7&*&$*&7*7&* ES
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myobath evoked concentration-dependent relaxation of KCl precontracted human bladder strips and at-tainedDVLJQL¿FDQWHIIHFWDWQDQRPRODUFRQFHQWUDWLRQ
UDQJH6RODEHJURQUHOD[HGWKHKXPDQEODGGHUVWULSV WKDWZHUHSUHFRQWUDFWHGZLWKP0.&OZLWKDS'2 YDOXHRIr)LJXUH
,VRSURWHUHQRODQRQVHOHFWLYHDGUHQRFHSWRU DJRQLVWSURGXFHGVLJQL¿FDQWUHOD[DWLRQRISUHFRQ -tracted muscle strips at >100ZKHUHDVVRODEHJURQ
SURGXFHGVLJQL¿FDQWUHOD[DWLRQDW!0 )LJXUH)LJXUH :KHQ FRPSDUHG ZLWK SURFDWHURO D VHOHFWLYH :KHQFRPSDUHGZLWKSURFDWHURODVHOHFWLYH DJRQLVW VRODEHJURQ SURGXFHG D VLJQL¿FDQW S VRODEHJURQ SURGXFHG D VLJQL¿FDQW S VRODEHJURQSURGXFHGDVLJQL¿FDQWS UHOD[DWLRQ )LJXUH 7KH S')LJXUH 7KH S')LJXUH7KHS'2 values were calculated
IURPWKHFRQFHQWUDWLRQUHOD[DWLRQFXUYHZHUH
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LVRSURWHUHQRODQGVRODEHJURQ UHVSHFWLYHO\UHVSHFWLYHO\
,QRWKHUH[SHULPHQWVHI¿FDF\RIVRODEHJURQ
to relax human bladder contraction in response to
HOHFWULFDO¿HOGVWLPXODWLRQ()6DWWKHORZHUIUHTXHQFLHV DQG+]ZDVFRPSDUHGDJDLQVWLVRSURWHUHQROLVRSURWHUHQRO 'UXJVZHUHLQFXEDWHGIRUPLQLQWKHP\REDWK SULRUWRWHVWLQJWKHLUHIIHFWRQ()6)LJXUH7KHUH ZDVDVLJQL¿FDQWLQKLELWLRQRIGHWUXVRUFRQWUDFWLRQ DW+]E\VRODEHJURQDQGLVRSURWHUHQRODW0 )LJXUH DQG WKH GHWUXVRU UHVSRQVH ZDV UHGXFHG DWDOOIUHTXHQFLHV+RZHYHUPD[LPXPVXSSUHVVLRQ ZDVREVHUYHGDW()6LQGXFHGFRQWUDFWLRQVRIORZHU IUHTXHQFLHVDV+]7KHIRUFHIUHTXHQF\FXUYHZDV
shifted to the right by both solabegron and isoprotere- isoprotere-nol, at 10, at 100WKHSHUFHQWDJHHIIHFWEHFRPHVLPLODUIRU
IUHTXHQFLHVRI+](I¿FDF\RIVRODEHJURQZDV VOLJKWO\EHWWHUWKDQLVRSURWHUQROLQVXSSUHVVLQJ()6 HYRNHGFRQWUDFWLRQEXWQRWVWDWLVWLFDOO\VLJQL¿FDQW
COMMENTS
$ SUHYLRXV VWXG\ E\ <DPDJXFKL KDV GHWHU$SUHYLRXVVWXG\E\<DPDJXFKL KDV GHWHU<DPDJXFKLKDV GHWHUhas deter-
deter-PLQHGWKHUHODWLYHDEXQGDQFHRIDQGDG -renoceptor in the human bladder, but the anatomicalthe human bladder, but the anatomicalhuman bladder, but the anatomicalbladder, but the anatomicalanatomical distribution of expression in bladder in terms of of expression in bladder in terms of urothelium and detrusor has not been determined
,QRXUVWXG\ZHGHPRQVWUDWHGH[SUHVVLRQRIDOO WKUHH DGUHQRFHSWRUV P51$V XURWKHLXP DV ZHOODGUHQRFHSWRUV P51$V XURWKHLXP DV ZHOODGUHQRFHSWRUV P51$V XURWKHLXP DV ZHOO DVLQGHWUXVRUPXVFOHVRIWKHKXPDQEODGGHU 7KH The
IXQFWLRQDOLPSRUWDQFHRIDGUHQRFHSWRUV H[SUHVVHG-adrenoceptors expressed
LQXURWKHOLXPUHPDLQVWREHFRPSOHWHO\LQYHVWLJDWHG ,WLVLQWHUHVWLQJWRQRWHWKDWHIIHFWRIDGUHQRFHSWRUV
agonists on micturition is mediated principally by
WKHVHUHFHSWRUV
7KHHIIHFWRI6RODEHJURQRQKXPDQEODGGHU VWULSVZDVUHFHQWO\UHSRUWHG2XU UHVXOWV RQ WKHOur results on the
HIIHFW RI VDPH GUXJ 6RODEHJURQ RQ KXPDQ EODG -der generally agree with the earlier study showing relaxation of human detrusor strip pre-contracted
ZLWK FDUEDFKRO +RZHYHU WKH IHZ QRWDEOHfew notable
Figure 2 – H & E staining of surgically separated tissue of detrusor (Panel A) and urothelium (Panel B). Absence of any smooth muscle cells in urothelium section verify lack of con-tamination from detrusor in the expression studies demonstrated in Figure-1.
A
differences are the use of different stimuli of KCl to evoke contraction prior to the addition of solabegron
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contracted muscle strips were produced at much
lower concentration of 10 0 DV DJDLQVW 0
UHSRUWHGIRUUHOD[DWLRQRIFDUEDFKROWRQH$QRWKHU PDMRUGLIIHUHQFHEHWZHHQWKHWZRVWXGLHVRQKXPDQ
bladder was the lack of difference observed in this
VWXG\ZLWKUHVSHFWWRWKHVXSSUHVVLRQRI()6LQGXFHG GHWUXVRUFRQWUDFWLRQ%LHUVHWDOUHSRUWHGWKDWRQO\ VRODEHJURQZDVDEOHWRVXSSUHVV()6FRQWUDFWLRQDW
100ZKHUHDVZHREVHUYHGWKDWLVRSURWHUQROZDV
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different experimental methodology followed in the
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measured prior to testing of drugs and no drugs were
DGGHGWRP\REDWKEHIRUH()6ZDVGRQH:KHUHDVWKH SUHYLRXVVWXG\WKHWLVVXHVWULSVZHUHVXEMHFWHGWR
carbachol 100FRQWUDFWLRQSULRUWR()6UHVSRQVH
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explain different results, there could be differences in the sensitivities of bladder specimens used in the two
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(YLGHQFH VXJJHVWV WKDW DGUHQRFHSWRUDGUHQRFHSWRU
activation by isoproterenol in rat urothelial cells can
WULJJHUSURGXFWLRQDQGUHOHDVHRI12GXHWRDQLQFUHDVH Figure 3 – Concentration dependent relaxation of the KCl-induced tone of human detrusor strips by Solabegron, Procaterol and Iso-proterenol. Relaxation evoked by drugs in muscle strips pre-contracted with 30nM KCl is expressed as percentage of the relaxation
LQGXFHGE\0SDSDYHULQH9DOXHVDUHH[SUHVVHGDVWKHPHDQ6(0DQGVLJQL¿FDQWGLIIHUHQFHIURPFRQWUROZDVFRQVLGHUHGDWS 'RVHUHVSRQVHFXUYHZHUHHYDOXDWHGE\VLJPRLGFXUYH¿WWLQJDQGORJ(&YDOXHVS'2) were calculated by non-linear regression
analysis using Graph Pad Prism.
Figure 4 – A representative trace for the response of a human detrusor strip to EFS (5, 10, 15 Hz) in the presence of oxygenated Krebs’ solution, and after 20 min incubation in Solabegron and Isoproterenol (10Isoproterenol (10 (10-8-10-4 M). Both the drugs suppressed
EFS evoked detrusor contraction at 10-4 M concentration. The
in intracellular Ca2+ following activation of the DGHQ\ODWHF\FODVHSDWKZD\LQWKHXURWKHOLDOFHOOV ,WKDVEHHQUHSRUWHGWKDWLQWUDYHVLFDODGPLQLVWUDWLRQ RI12VFDYHQJHUGHFUHDVHGEODGGHUFDSDFLW\LQGXFLQJ EODGGHUFRQWUDFWLRQVDQGWKDWDQLQWUDYHVLFDOO\ DSSOLHG 12 GRQRU GHFUHDVHG EODGGHU RYHUDFWLYLW\
induced by a chemical irritant, cyclophosphamide in
UDWV&RQVLGHULQJWKHPLQLPDOUHOD[LQJHIIHFWVRI 12RQUDWEODGGHUVPRRWKPXVFOHV LW LV EHOLHYHG; it is believed
WKDWHIIHFWRI12RQUHÀH[EODGGHUDFWLYLW\LVPXFK
better explained by suppression of excitability of and/or the release of transmitters from bladder afferent
QHUYHV7KXVLWVHHPVUHDVRQDEOHWRDVVXPHWKDW
information about E-adrenoceptors expressed in the human urothelium might be involved in the regulation
RIEODGGHUVHQVRU\IXQFWLRQV
6WXGLHVKDYHVKRZQWKDWVWLPXODWLRQRI E2--and E3-adrenergic receptors existing in the human detrusor can produce direct relaxation of the detrusor smooth muscle without blocking voiding induced
EODGGHUFRQWUDFWLRQ7KLV E-adrenergic-stimu-lated relaxation is mediated through the stimulation
RIDGHQ\OF\FODVHDQGWKHDFFXPXODWLRQRIF\FOLF$03 7KHLQYROYHPHQWRIE3-adrenoceptor activation in mediating the relaxation of human detrusor by E3-adrenoceptor agonists was demonstrated by lackadrenoceptor agonists was demonstrated by lack agonists was demonstrated by lack of suppression of its effect by selective E1 and/or and/or E2-adrenoceptor antagonists such as dobutamine and-adrenoceptor antagonists such as dobutamine and
SURFDWHURO7KHUROHRIE3-adrenoceptor is further
YHUL¿HGE\WKHEORFNDGHRI6RODEHJURQHYRNHGUHOD[ -ation by selective EDGUHQRFHSWRU DQWDJRQLVWVDGUHQRFHSWRUDQWDJRQLVWV
Considering the role of E3-adrenoceptors in modulating the control of bladder smooth muscle tone in humans; these results support the hypothesis that E$5 DJRQLVWV UHSUHVHQW$5DJRQLVWVUHSUHVHQWa useful clinical strategy for
WUHDWLQJGHWUXVRURYHUDFWLYLW\E-adrenoceptoradrenoceptor antagonists blockers have also been advocated for stress urinary incontinence owing to inappropriate
UHÀH[XUHWKUDOUHOD[DWLRQEHFDXVHSURSUDQROROSUH -vents the reduction in urethral pressure after sacral
URRWVWLPXODWLRQ+RZHYHUE-adrenoceptor an-adrenoceptor an- an-tagonists are not particularly useful in treating bladder
RUXUHWKUDOGLVRUGHUV&XUUHQWO\WKHUDS\IRUWKH 2$%V\QGURPHVXFKDVZLWKDQWLPXVFDULQLFDJHQWV
or direct acting smooth muscle relaxants, can produce the result of urinary retention and other mechanistic
VLGHHIIHFWV
CONCLUSIONS
The present study demonstrates that stimula-tion of EUHFHSWRUZLWK6RODEHJURQHYRNHVKXPDQ
bladder relaxation, suggesting that selective E3-adre-noceptor agonist may be a valuable new treatment for
WKH2$%V\QGURPH7KHH[SUHVVLRQRIE1-,E2- and E3-adrenoceptors in urothelium apart from detrusor may suggest additional mechanism of action for the EDGUHQRFHSWRULQWKHORZHUXULQDU\WUDFW
CONFLICT OF INTEREST
This work was supported in part by
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REFERENCES
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Accepted after revision: November 17, 2008
Correspondence address:
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EDITORIAL COMMENT
Recent interest of the bladder physiology has focused on urothelial/suburothelial cells of the
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urothelium and the detrusor of human bladder, and
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subtypes are functionally expressed in the urinary
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0XOWLSOHOLQHVRIHYLGHQFHVXJJHVWWKDWȕ3 -adrenoceptors are predominantly abundant in the human detrusor muscle of the urinary bladder, and play important roles in detrusor relaxation during
uri-QDU\VWRUDJHLQKXPDQV%HVLGHVLWLVSRVWXODWHGWKDW ȕ3-adrenoceptor agonists could be highly promising
agents to treat overactive bladder by a clinical trial
,QWKHQHDUIXWXUH,KRSHQRYHO¿QGLQJVRI PHFKDQLVPRIWKHXURWKHOLDOVXEXURWKHOLDOȕDGUHQR -ceptor subtypes in the urinary bladder may shed light on the pathological conditions such as overactive
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REFERENCES
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