α1-Adrenoceptor pharmacome: α1L-Adrenoceptor and α1A-adrenoceptor in the lower urinary tract

α₁‐Adrenoceptors are involved in physiological functions such as urinary excretion and ejaculation in the lower urinary tract (LUT). Several α₁ antagonists are clinically used for the treatment of urinary obstruction in patients with benign prostatic hyperplasia. At present, three classical α₁‐adrenoceptor subtypes (α_1A, α_1B, and α_1D) have been identified, among which the α_1A and α_1D‐adrenoceptor subtypes have been regarded as the main targets of α₁ antagonist therapy for LUT symptoms. Prazosin has been used as a prototypic, classical antagonist, to characterize α₁‐adrenoceptors pharmacologically, (i.e. all classical α₁‐adrenoceptor subtypes show high‐affinity for the drug). However, we found that α₁‐adrenoceptors in the LUT show atypical low‐affinity for prazosin. Therefore, the concept α_1L‐receptor, which indicates α₁‐adrenoceptor(s) showing low‐affinity for prazosin has been introduced. A recent study demonstrated that the α_1L‐adrenoceptor is a specific phenotype present in the many intact tissues including human LUT, and that it originates from the ADRA1A gene. Therefore, the α_1L‐adrenoceptor in the LUT is now re‐defined as α_1A(L)‐adrenoceptor. The physiological and pharmacological difference between classical α_1A(H), and α_1A(L) which is the native receptor expressed in the LUT is of special interest as it provides fundamental bases for urological α_1A‐adrenoceptor blocking pharmacotherapy. Here, we briefly review the α₁‐adrenoceptors in the LUT with special reference to phenotype‐based (pharmacome) analysis.