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ヒト膀胱上皮におけるβ-アドレナリン受容体の発現と機能的役割 Expression and functional role of β-adrenoceptors in the human urinary bladder urothelium Otsuka, Atsushi human urothelium β-adrenoceptor agonist mucosa β3-adrenoceptor bladder nitric oxide 浜松医科大学 博士（医学） 浜松医科大学学位論文 医博論第456号(平成20年7月18日） doctoral 医学系研究科 We investigated the presence of β-adrenoceptor subtypes in human urinary bladder urothelium and examined whether β-adrenoceptors in the urothelium modulate the relaxation responses of isolated human detrusor strips to a β-adrenoceptor agonist. Expression of β1-, β2- and β3-adrenoceptor mRNA in urothelium and detrusor smooth muscle was determined by reverse transcription-polymerase chain reaction (RT-PCR), and the distribution of β1-, β2- and β3-adrenoceptors in human urinary bladder urothelium was examined by immunohistochemistry. Paired human longitudinal detrusor strips with and without an intact urothelium were suspended in organ baths to construct concentration-response curves to isoproterenol. The possible involvement of urothelium-derived nitric oxide (NO) in this response was examined in additional experiments with urothelium-intact strips in the presence of NG-nitro-L-arginine methylester (L-NAME). Results confirmed the expression of β1-, β2- and β3-adrenoceptors in the human urinary bladder urothelium. Further, the presence of the urothelium caused a parallel rightward shift of the concentration-response curve to isoproterenol, with a significant reduction in potency (pEC50). L-NAME failed to exert any significant effect on the relaxation response to isoproterenol in the urothelium-intact strips. These results confirm the presence of β1-, β2- and β3-adrenoceptors in human urinary bladder urothelium. Further, they suggest that urothelial β-adrenoceptors induce the release of a urothelium-derived factor which inhibits the β-adrenoceptor agonist-induced relaxation of the human detrusor smooth muscle, and that this inhibitory mechanism might not involve NO. doctoral thesis Springer 2008-06 2008-07-18 AM application/pdf Naunyn-Schmiedeberg's Archives of Pharmacology 4-6 377 473 481 乙第456号 0028-1298 1432-1912 https://hama-med.repo.nii.ac.jp/record/802/files/DT_ron456ronbun.pdf http://hdl.handle.net/10271/833 https://hama-med.repo.nii.ac.jp/records/802 eng 18311486 https://doi.org/10.1007/s00210-008-0274-y Copyright Springer-Verlag 2008 open access