Investigations into the presence of functional Beta1, Beta2 and Beta3-adrenoceptors in urothelium and detrusor of human bladder.
OBJECTIVE
We investigated the presence of functional Beta1, Beta2 and Beta3-adrenoceptor in urothelium and detrusor muscle of human bladder through in vitro pharmacology of selective Beta3 adrenoceptor agonist solabegron.


METHODS
Expression of these adrenoceptors in surgically separated human urothelium and detrusor muscle were investigated using RT-PCR. The effects of activating these receptors were studied by determining the relaxation produced by Beta-adrenoceptors agonist in pre-contracted human detrusor strips.


RESULTS
The results confirmed the presence of mRNA for Beta1, Beta2 and Beta3-adrenoceptor in both human urothelium and detrusor. In an in vitro functional bladder assay, Solabegron and other agonists for Beta-adrenoceptors such as procaterol and isoproterenol evoked potent concentration-dependent relaxation of isolated human bladder strips with pD2 values of 8.73 +/- 0.19, 5.08 +/- 0.48 and 6.28 +/- 0.54, respectively.


CONCLUSIONS
Selective Beta3-adrenoceptor agonist may be a potential new treatment for the overactive bladder OAB syndrome. Existence of Beta3-adrenoceptor mRNA exists in the urothelium in addition to the detrusor muscle suggest multiple site of actions for the Beta3-adrenoceptor in the lower urinary tract.
Tyagi
Pradeep
P
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. pradeep.tyagi@beaumont.edu
Thomas
Catherine A
CA
Yoshimura
Naoki
N
Chancellor
Michael B
MB
D000293:Adolescent; D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001713:Biphenyl Compounds; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000814:Aniline Compounds; D001565:Benzoates; D001713:Biphenyl Compounds; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; C523977:solabegron