Mechanical Function and Gene Expression of ⍺1-Adrenoceptor Subtypes in Dog Intravesical Ureter - 06/08/11
, Yoshitaka Tomiyama a, Yuji Hoyano a, Yoshinobu Yamazaki a, Hiroshi Kusama a, Yasue Kubota b, Shoichi Sasaki b, Kenjiro Kohri b
Reprint requests: Shinya Kobayashi, Pharmacology Research and Development, Kissei Pharmaceutical Company, Limited, 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304 JapanRésumé |
Objectives |
To characterize the contractile functions and gene expression of the ⍺1-adrenoceptor (AR) subtypes present in the dog intravesical ureter.
Methods |
In a functional study, ⍺1-AR antagonists were evaluated against phenylephrine (⍺1-AR agonist)-induced contractions in dog isolated intravesical ureteral preparations. The quantitative expression of ⍺1-AR subtype mRNA in this tissue was determined using real-time quantitative reverse transcriptase-polymerase chain reaction.
Results |
In the isolated intravesical ureter, prazosin (nonselective ⍺1-AR antagonist), silodosin (selective ⍺1A-AR antagonist), naftopidil (selective ⍺1D-AR antagonist), and BMY-7378 (selective ⍺1D-AR antagonist) all shifted the concentration-contractile response curve for phenylephrine to the right. The rank order of potencies (pKB value) was silodosin (9.45 ± 0.14), prazosin (8.16 ± 0.08), naftopidil (7.39 ± 0.19), and BMY-7378 (6.78 ± 0.20). The ⍺1A-AR antagonist silodosin was much more potent than the 2 ⍺1D-AR antagonists. The rank order of mRNA expression levels among the ⍺1-AR subtypes was ⍺1d (72.68%), ⍺1a (24.14%), and ⍺1b (3.18%).
Conclusions |
In the dog intravesical ureter, ⍺1A-AR plays a major role in contraction, despite the prevalence of ⍺1D-AR.
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Vol 74 - N° 2
P. 458-462 - août 2009 Retour au numéro
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