PTHrP is endogenous relaxant for spontaneous smooth muscle contraction in urinary bladder of female rat.

• Nishikawa, Nobuyuki

• Kanematsu, Akihiro

• Negoro, Hiromitsu

• Imamura, Masaaki

• Sugino, Yoshio

• Okinami, Takeshi

• Yoshimura, Koji

• Hashitani, Hikaru

• Ogawa, Osamu

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.

Journal

• Endocrinology

  Endocrinology 154 (6), 2058-2068, 2013-06

  Endocrine Society

Keywords

• Animals
• Carbachol/pharmacology
• Cells, Cultured
• Cholinergic Agonists/pharmacology
• Cyclic AMP/metabolism
• Female
• Gene Expression Profiling
• Immunoblotting
• Muscle Contraction/genetics
• Muscle Contraction/physiology
• Muscle, Smooth/metabolism
• Muscle, Smooth/physiopathology
• Myocytes, Smooth Muscle/drug effects
• Myocytes, Smooth Muscle/metabolism
• Oligonucleotide Array Sequence Analysis
• Parathyroid Hormone-Related Protein/genetics
• Parathyroid Hormone-Related Protein/metabolism
• Parathyroid Hormone-Related Protein/physiology
• Peptide Fragments/pharmacology
• Rats
• Rats, Sprague-Dawley
• Receptor, Parathyroid Hormone, Type 1/genetics
• Receptor, Parathyroid Hormone, Type 1/metabolism
• Receptor, Parathyroid Hormone, Type 1/physiology
• Reverse Transcriptase Polymerase Chain Reaction
• Urinary Bladder/metabolism
• Urinary Bladder/physiopathology
• Urinary Retention/genetics
• Urinary Retention/metabolism
• Urinary Retention/physiopathology

Details

• CRID: 1050564285750284032
• NII Article ID: 120005477201
• NII Book ID: AA00635074
• ISSN: 00137227
• HANDLE: 2433/189845
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles