alpha1-ADRENERGIC RECEPTOR SUBTYPES IN HUMAN DETRUSOR

Abstract

Human detrusor contained two alpha1AR subtypes (alpha1d > alpha1a), a finding that is different from rat, another commonly used animal model. Since non-subtype selective alpha1AR antagonists ameliorate irritative bladder symptoms (in men and women with/without outlet obstruction), and Rec 15/2739 (alpha1a selective antagonist) does not improve symptom scores in BPH, our findings suggest bladder alpha1dARs may provide a potentially novel mechanism underlying these therapeutic benefits.

A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

“…The fast relief of the bothersome storage symptoms with tamsulosin could be related to the fact that it may reduce not only bladder overactivity due to a reduction of bladder wall hypertrophy secondary to improving obstruction (which is a longer term process), but also bladder overactivity due to direct blockade of (upregulated) a 1D -ARs in the bladder and/or in its innervating structures such as the spinal cord (which is a more immediate process). [14][15][16] The results of this trial are in line with other data in the literature. Other a 1 -AR antagonists appear to have similar efficacy in improving symptoms and urinary flow.…”

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

“…Various a1-adrenergic receptor subtypes have been identified in the lower urinary tract, including a1A and a1D receptors in prostatic stromal cells, 26,27 a1B receptors in epithelial cells, a1A and a1B receptors in vascular smooth muscle, 28 a1A and a1D receptors in the urethra and bladder and a1D receptors in the detrusor muscle. 29 Penile erection and flaccidity depend on a balance between contraction and relaxation of the corpus cavernosum smooth muscle. 30 In various forms of ED, the balance favors smooth muscle contraction rather than relaxation.…”

Safety and efficacy of tamsulosin in the treatment of painful ejaculation: a randomized, double-blind, placebo-controlled study

“…[21][22][23][24][25] Another study demonstrates that a 1 -adrenoceptors in the human detrusor are of the a 1D and, to a lesser extent, the a 1A subtypes. 26 Tamsulosin is an a 1 -adrenoceptor antagonist that exhibits selectivity for a 1A -and, somewhat lesser extent, a 1D -over a 1B -adrenoceptors. [26][27][28][29] In addition, tamsulosin has 12 times greater affinity for a 1 -adrenoceptors in the human prostate than in the aorta in contrast to prazosin, which has comparable affinity for those in the prostate and aorta.…”