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

Area of Science:

• Pharmacology
• Urology
• Molecular Biology

Context:

• Adrenergic receptors (ARs), a G protein-coupled receptor family, are classified into α1, α2, and β types.
• α1 ARs are implicated in the pathophysiology of various urinary tract (UT) dysfunctions.
• Expression patterns of α1 ARs vary across different regions of the human UT, including the ureter, bladder, prostate, and urethra.

Purpose:

• This review focuses on α1 ARs and their antagonists, particularly in the context of UT disorders.
• To explore the differential expression of α1 AR subtypes (α1A, α1B, α1D) within the human UT.
• To discuss the concept of uroselectivity for α1 AR antagonists in treating lower UT symptoms.

Summary:

• α1 ARs exhibit distinct expression patterns in the ureter (distal > medial = proximal) and bladder (trigone, detrusor, neck), providing a basis for therapeutic interventions.
• Benign prostatic hyperplasia (BPH) research heavily investigates α1 AR expression in the prostate and detrusor.
• Studies indicate α1A and α1D AR subtypes are more prevalent in the UT than α1B, driving interest in selective antagonists.

Impact:

• The differential expression of α1 ARs supports the use of antagonists in conditions like distal ureter calculi expulsive therapy.
• Understanding subtype-specific expression, particularly α1A/D selectivity, is vital for developing targeted therapies for lower UT symptoms and BPH.
• The concept of uroselectivity, defined by efficacy in urinary muscle contraction and minimal cardiovascular effects, guides the development of safer and more effective α1 AR antagonist drugs.