Mechanical function and gene expression of alpha(1)-adrenoceptor subtypes in dog intravesical ureter.
OBJECTIVE
To characterize the contractile functions and gene expression of the alpha(1)-adrenoceptor (AR) subtypes present in the dog intravesical ureter.


METHODS
In a functional study, alpha(1)-AR antagonists were evaluated against phenylephrine (alpha(1)-AR agonist)-induced contractions in dog isolated intravesical ureteral preparations. The quantitative expression of alpha(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 alpha(1)-AR antagonist), silodosin (selective alpha(1A)-AR antagonist), naftopidil (selective alpha(1D)-AR antagonist), and BMY-7378 (selective alpha(1D)-AR antagonist) all shifted the concentration-contractile response curve for phenylephrine to the right. The rank order of potencies (pK(B) 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 alpha(1A)-AR antagonist silodosin was much more potent than the 2 alpha(1D)-AR antagonists. The rank order of mRNA expression levels among the alpha(1)-AR subtypes was alpha(1d) (72.68%), alpha(1a) (24.14%), and alpha(1b) (3.18%).


CONCLUSIONS
In the dog intravesical ureter, alpha(1A)-AR plays a major role in contraction, despite the prevalence of alpha(1D)-AR.
Kobayashi
Shinya
S
Kissei Pharmaceutical Company, Limited, Nagano, Japan. shinya_kobayashi@pharm.kissei.co.jp
Tomiyama
Yoshitaka
Y
Hoyano
Yuji
Y
Yamazaki
Yoshinobu
Y
Kusama
Hiroshi
H
Kubota
Yasue
Y
Sasaki
Shoichi
S
Kohri
Kenjiro
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D014513:Ureter / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D011224:Prazosin