Characterization of α, β, and muscarinic receptor distribution in porcine ureters: a translational model for pharmacological ureteral dilation.

Intraoperative ureteral dilation through smooth muscle relaxation is of interest for improving upper urinary tract access during retrograde intrarenal surgery. Porcine ureters are widely used translational models due to their anatomical similarities to humans; however, the distribution of receptors essential for pharmacological feasibility studies has not been fully characterized. This ex vivo study defines the regional expression of adrenergic and muscarinic receptors throughout the porcine ureter. Ureters from juvenile female Yorkshire swine (n = 4) were segmented into renal pelvis, proximal, middle, distal, and bladder cuff regions. Immunohistochemical (IHC) and histomorphometric analyses evaluated protein expression of α- and β-adrenergic receptor subtypes and muscarinic (M) subtypes. Quantitative-PCR assessed mRNA expression across ureteral regions; statistical analyses were performed using the Kruskal-Wallis test (IHC) and the Friedman test (qPCR), with Dunn's post hoc correction (P < 0.05). IHC demonstrated uniform distribution of α-, β-, M3, and M5 subtypes (P > 0.05). M1 expression was significantly higher in distal and bladder cuff regions versus proximal ureter (P = 0.0262), while M2 was elevated in the renal pelvis (P = 0.0134). All subtypes showed lower proximal immunoreactivity, and M4 was scantily detected. Most receptors are localized to the urothelium, except M3, which was also present in smooth muscle. qPCR confirmed expression of all receptor families except M4, with no regional differences in α-adrenergic or muscarinic transcripts. β-2 expression exceeded β-3 (P = 0.0439), and β-adrenergic transcripts were significantly higher than muscarinic (P = 0.0429). These results provide essential biological context for advancing translational research on the ureter.NEW & NOTEWORTHY This study provides the first comprehensive quantitative characterization of adrenergic and muscarinic receptor distribution throughout the porcine ureter using qPCR and immunohistochemistry. Novel findings include the first quantification of all β-adrenoceptor subtypes, revealing β-2 dominance (74% of β-receptors, 54% of total transcripts), and detection of M1 muscarinic receptor mRNA. α-1a/1d codominance mirrors human ureters. Predominant urothelial receptor localization suggests epithelial smooth muscle signaling. These data strengthen the understanding of porcine ureteral physiology for clinical and translational studies.