Evidence for the presence of a1 adrenoreceptor subtypes in the human ureter

Aim: Several studies have proposed a role for a1 adrenoceptors (ARs) in ureteral physiology, indicating that they are present in the ureter; however, few studies have been done to identify a1 AR subtypes present in this area.Thus, this study was carried out to characterize the a1 AR subtype gene and protein expression in proximal, medial, and distal region of the human ureter. Methods: Molecular characterization of a1 AR subtypes were analyzed by semi-quantitative RT-PCR. a1 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. Results: Analysis of saturation binding curves revealed a heterogeneous distribution of a1 AR binding sites, the Bmax for the distal ureter was indeed 52.5 5.4 fmol/mg prot, while a lower similar density of a1 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 a1 AR subtypes indicated that each receptor was present, although with di¡erences in terms of the amount expressed. Conclusions: Human ureter was endowed with each a1 AR subtype, although a1D and a1A ARs were prevalent over a1B ARs. Radioligand binding results revealed that there were no signi¢cant di¡erences in the Kd between ureteral regions, while a heterogeneous distribution of a1 AR binding sites was detected, with the highest density of a1 ARs in the distal ureter and a lower similar density in the medial and proximal ureters.