title: PTHrP is endogenous relaxant for spontaneous smooth muscle contraction in urinary bladder of female rat.
abstract: Acute bladder distension causes various morphologic and functional changes, in part through altered gene expression. We aimed to investigate the physiologic role of PTHrP, which is up-regulated in an acute bladder distension model in female rats. In the control Empty group, bladders were kept empty for 6 hours, and in the Distension group, bladders were kept distended for 3 hours after an artificial storing-voiding cycle for 3 hours. In the Distention group bladder, up-regulation of transcripts was noted for 3 genes reported to be up-regulated by stretch in the cultured bladder smooth muscle cells in vitro. Further transcriptome analysis by microarray identified PTHrP as the 22nd highest gene up-regulated in Distension group bladder, among more than 27,000 genes. Localization of PTHrP and its functional receptor, PTH/PTHrP receptor 1 (PTH1R), were analyzed in the untreated rat bladders and cultured bladder cells using real-time RT-PCR and immunoblotting, which revealed that PTH1R and PTHrP were more predominantly expressed in smooth muscle than in urothelium. Exogenous PTHrP peptide (1-34) increased intracellular cAMP level in cultured bladder smooth muscle cells. In organ bath study using bladder strips, the PTHrP peptide caused a marked reduction in the amplitude of spontaneous contraction but caused only modest suppression for carbachol-induced contraction. In in vivo functional study by cystometrogram, the PTHrP peptide decreased voiding pressure and increased bladder compliance. Thus, PTHrP is a potent endogenous relaxant of bladder contraction, and autocrine or paracrine mechanism of the PTHrP-PTH1R axis is a physiologically relevant pathway functioning in the bladder.
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nishikawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kanematsu
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Negoro
authors.forename: Masaaki
authors.initials: M
authors.lastname: Imamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sugino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okinami
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Hikaru
authors.initials: H
authors.lastname: Hashitani
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015151:Immunoblotting; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001743:Urinary Bladder / Q000378:metabolism / Q000503:physiopathology*; D016055:Urinary Retention / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018679:Cholinergic Agonists; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D044168:Receptor, Parathyroid Hormone, Type 1; D002217:Carbachol; D000242:Cyclic AMP