Alpha1 adrenoceptors in human urinary tract:expression, distribution and clinical implications

Adrenergic receptors (ARs) are a class of proteins belonging to the G proteincoupled
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 α1 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.