EXPRESSION AND POSSIBLE FUNCTIONAL ROLE OF THE beta 3-ADRENOCEPTOR IN HUMAN AND RAT DETRUSOR MUSCLE

AbstractPurpose: To investigate the presence of the beta 3-adrenoceptor (beta 3-AR) in human and rat detrusor muscle and the usefulness of beta 3-AR agonists as drugs for the treatment of urinary frequency.Materials and Methods: FK175, ethyl [(S)-8-[(R)-2-(3-chlorophenyl)-2 -hydroxyethylamino]-6,7,8,9-tetrahydro-5H-benzocyclohepton-2-yloxy] acetate monohydrochloride monohydrate, was used as a beta 3-AR selective agonist. The expression of beta-AR subtypes (beta 1-, beta 2-, beta 3-AR) mRNA was investigated in rat and human detrusor muscle by RT-PCR. beta 3-AR agonist induced cyclic AMP (cAMP) levels were measured in rat detrusor muscle strips. The relaxation response produced by a beta 3-AR agonist was measured in a KCl induced tonic contraction model in rat detrusor muscle strips. The effect of a beta 3-AR agonist on urinary bladder function was investigated by cystometry using a conscious rat model of urinary frequency.Results: beta 3-AR mRNA was substantially expressed in both rat and human detrusor mu...