Characterization of α1-adrenoceptor Subtypes Mediating Contraction in Human Isolated Ureters

OBJECTIVES To characterize the contractile functions of the alpha(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 alpha(1)-AR agonist or antagonist were excluded from this study. The effects of alpha(1)-AR antagonists against phenylephrine (alpha(1)-AR agonist)-induced contractions were evaluated in human isolated ureteral preparations. RESULTS Pooled data from all ureters showed that phenylephrine (alpha(1)-AR agonist) induced a concentration-dependent tonic contraction (pD(2) value, 4.92 +/- 011). The phenylephrine-induced maximum contraction was significantly greater in lower ureters than in upper ones. Prazosin (non-selective alpha(1)-AR antagonist), silodosin (selective alpha(1A)-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 in all ureters (pK(B) values) being silodosin (9.72 +/- 0.14) > prazosin (8.64 +/- 0.08) > BMY-7378 (7.04 +/- 0.14). The alpha(1A)-AR antagonist silodosin was thus much more potent than the other 2 antagonists. CONCLUSIONS Our results suggest that among alpha(1)-ARs, the alpha(1A) subtype plays the major role in contraction in the human ureter. UROLOGY 77: 762.e13-762.e17, 2011. Crown Copyright (C) 2011 Published by Elsevier Inc.