Alpha1 Adrenoceptors in Human Urinary Tract: Expression,Distribution and Clinical Implications

Abstract

Adrenergic receptors (ARs) are a class of proteins belonging to the G protein-coupled receptor family. Pharmacological and molecular studies allowed dividing ARs into three different categories: α1, α2 and β. In this review, we focused on α1 ARs and α1 AR antagonists, since α 1 ARs play an important role in the pathophysiology of a number of urinary tract (UT) dysfunctions. α1 ARs are widely expressed in human UT; in particular, the three ureter areas (distal, medial and proximal) show different patterns of receptor expression (i.e. distal > medial = proximal), giving the molecular basis for the use of α1 ARs antagonist in the expulsive therapy of distal ureter calculi. Bladder areas are characterized by important differences among trigone, detrusor and neck, the first showing a different pattern of expression compared to the other parts. Further, there are evidences of both density and subtype gender-dependent expressions. α1 ARs expression in prostate and detrusor is a widely investigated area of research, mainly due to the clinical impact of benign prostatic hyperplasia (BPH). Urethra has not been well studied in human, although it plays a role in the control of continence.

Studies carried out on α1 AR subtype expression in the UT indicate that, although the presence of each subtype is observed, α1A firstly and then α1D ARs seem to be more expressed than α1B ARs. Thus, drugs that demonstrate high α1A/D AR selectivity have drawn the researchers’ attention. As it relates specifically to the α1 AR antagonists used in the treatment of lower UT symptoms, the concept of uroselectivity has been operationally defined; indeed, in a number of recent publications uroselectivity has been defined as the degree to which a given compound inhibits norepinephrine-induced increase in urinary muscle contractions and/or its propensity to generate unwanted cardiovascular effects, such as decreases in blood pressure.