Evidence for the presence of α1 adrenoceptor subtypes in the human ureter

Abstract

Several studies have proposed a role for alpha1 adrenoceptors (ARs) in ureteral physiology, indicating that they are present in the ureter; however, few studies have been done to identify alpha1 AR subtypes present in this area. Thus, this study was carried out to characterize the alpha1 AR subtype gene and protein expression in proximal, medial, and distal region of the human ureter. Molecular characterization of alpha1 AR subtypes were analyzed by semi-quantitative RT-PCR. alpha1 AR protein expression was studied by saturation binding curves and by competition binding curves with selective antagonists. Analysis of data was performed using the GraphPad PRISM 4 software. Analysis of saturation binding curves revealed a heterogeneous distribution of alpha1 AR binding sites, the B(max) for the distal ureter was indeed 52.5 +/- 5.4 fmol/mg prot, while a lower similar density of alpha1 ARs was demonstrated in the medial (25.2 +/- 1.7 fmol/mg prot) and proximal (23.4 +/- 0.4 fmol/mg prot) ureters. Molecular and pharmacological characterization of alpha1 AR subtypes indicated that each receptor was present, although with differences in terms of the amount expressed. Human ureter was endowed with each alpha1 AR subtype, although alpha1D and alpha1A ARs were prevalent over alpha1B ARs. Radioligand binding results revealed that there were no significant differences in the K(d) between ureteral regions, while a heterogeneous distribution of alpha1 AR binding sites was detected, with the highest density of alpha1 ARs in the distal ureter and a lower similar density in the medial and proximal ureters.