Characterization of ⍺1-adrenoceptor Subtypes Mediating Contraction in Human Isolated Ureters - 20/08/11
, Yoshitaka Tomiyama b, Shinya Kobayashi b, Yoshiyuki Kojima a, Yasue Kubota b, Kenjiro Kohri b
Reprint requests to: Shoichi Sasaki, M.D., Ph.D., Nagoya City University Graduate School of Medical Sciences, Department of Nephro-urology, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanRésumé |
Objectives |
To characterize the contractile functions of the ⍺1-adrenoceptor (AR) subtypes present in the human ureter.
Methods |
Specimens were taken from patients with renal cancer (“upper ureters;” n = 51) or bladder cancer (“lower ureters;” n = 23) who had not been treated by chemotherapy, radiation therapy, or immunotherapy before surgery. Patients systemically taking an ⍺1-AR agonist or antagonist were excluded from this study. The effects of ⍺1-AR antagonists against phenylephrine (⍺1-AR agonist)–induced contractions were evaluated in human isolated ureteral preparations.
Results |
Pooled data from all ureters showed that phenylephrine (⍺1-AR agonist) induced a concentration-dependent tonic contraction (pD2 value, 4.92 ± 011). The phenylephrine-induced maximum contraction was significantly greater in lower ureters than in upper ones. Prazosin (nonselective ⍺1-AR antagonist), silodosin (selective ⍺1A-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 in all ureters (pKB values) being silodosin (9.72 ± 0.14) > prazosin (8.64 ± 0.08) > BMY-7378 (7.04 ± 0.14). The ⍺1A-AR antagonist silodosin was thus much more potent than the other 2 antagonists.
Conclusions |
Our results suggest that among ⍺1-ARs, the ⍺1A subtype plays the major role in contraction in the human ureter.
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Vol 77 - N° 3
P. 762.e13-762.e17 - mars 2011 Retour au numéro
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