Abstract
BackgroundIt has been shown that hosphodiesterases (PDEs) play an important role in mediating the smooth muscle tone of rat urinary bladder. However, the gene expression profiles of them were still unknown.MethodsUrinary bladder Strips were obtained from both neonatal and adult Sprague-Dawley rats. RT-PCR/western blot and organ bath were used to measure the expression and function of PDEs.ResultsAdult rat urinary bladder expressed various PDE mRNA with the following rank order: PDE5A ≈ PDE9A ≈ PDE10A > PDE2A ≈ PDE4A ≈ PDE4D > PDE4B ≈ PDE3B ≈ PDE8B ≈ PDE7A ≈ PDE7B > PDE1A. PDE1B, PDE1C, PDE3A, PDE4C, PDE8A, and PDE11A were not detected. Of interest, the mRNA and protein of PDE3A were significantly decreased in adult rat urinary bladder compared to neonatal rat urinary bladder. Cilostamide, a specific inhibitor for PDE3, significantly inhibited the amplitude and frequency of carbachol-enhanced phasic contractions of neonatal rat bladder strips by 38.8% and 12.1%, respectively. Compared to the neonatal rat bladder, the effect of cilostamide was significantly blunted in adult rat urinary bladder: the amplitude and frequency of carbachol-enhanced phasic contractions were decreased by 13.4% (P < 0.01 vs neonatal rat bladder) and 4.4%, respectively. However, the mRNA and the protein levels of PDE3B were similar between neonatal and adult rat bladder.ConclusionWe found that several PDE isoforms were expressed in the rat urinary bladder with distinct levels. Moreover, we showed that the function of PDE3 was blunted in adult rat bladder likely due to the decreased expression of PDE3A.
Highlights
It has been shown that hosphodiesterases (PDEs) play an important role in mediating the smooth muscle tone of rat urinary bladder
Using RT-Polymerase chain reaction (PCR) technique, we determined the mRNA levels of 18 different PDE isoforms in adult rat urinary bladder
In contrast to our previous finding that PDE3A was highly expressed in neonatal rat bladder [2], PDE3A mRNA was not detected in adult rat urinary bladder
Summary
It has been shown that hosphodiesterases (PDEs) play an important role in mediating the smooth muscle tone of rat urinary bladder. Artim et al showed that PDE5 mediated the phasic contractions of neonatal rat bladder through nitric oxide-cGMP- protein kinase G pathway [1]. One of the most important features of the urinary detrusor smooth muscle is its ability to generate considerable phasic contractions [1, 2, 5]. These spontaneous phasic contractions change markedly with age [5]: during the first 2–3 weeks of life, they are characterized by highamplitude low-frequency spontaneous contractions; they turn into low-amplitude high-frequency pattern characteristic of normal adult rat.
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