Characterization of α 1-adrenoceptor Subtypes Mediating Contraction in Human Isolated Ureters

Abstract

To characterize the contractile functions of the α(1)-adrenoceptor (AR) subtypes present in the human ureter. 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 α(1)-AR agonist or antagonist were excluded from this study. The effects of α(1)-AR antagonists against phenylephrine (α(1)-AR agonist)-induced contractions were evaluated in human isolated ureteral preparations. Pooled data from all ureters showed that phenylephrine (α(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 (nonselective α(1)-AR antagonist), silodosin (selective α(1A)-AR antagonist), and BMY-7378 (selective α(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 α(1A)-AR antagonist silodosin was thus much more potent than the other 2 antagonists. Our results suggest that among α(1)-ARs, the α(1A) subtype plays the major role in contraction in the human ureter.