Alpha 1 adrenoceptor subtypes in human urinary bladder: Sex and regional comparison

Abstract

A detailed study of the presence of α 1 AR binding sites and α 1 AR subtype mRNA expression in human urinary bladder areas involved in the micturition (i.e. detrusor, trigone and neck) is reported here, investigating whether or not there are differences between sexes. Results obtained indicated that α 1 AR proteins were detectable in each bladder area. In both sexes, the detrusor and the neck expressed similar levels of α 1 ARs: respectively, detrusor: 14.6 ± 1.2 in men and 13.1 ± 1.1 fmol/mg prot in women; neck: 16.9 ± 3.2 in men and 17.5 ± 4.1 fmol/mg prot in women. In the trigone, significantly higher α 1ARs were found in women compared to men (20.6 ± 1.1 vs 11.7 ± 0.7 fmol/mg prot). Subtype analysis indicated that in women, each area was endowed with mRNA encoding for each α 1 AR subtype. The men detrusor expressed α 1a and α 1d ARs, while in the trigone and the neck, each subtype was present. Since the detrusor muscle hypertrophy is a marker of bladder obstructive outlet, the selective α 1 AR subtype targeting arouses much interest, as evidence indicates that there are differences in signalling pathways among the subtypes. Furthermore, the significance of the α 1 ARs coexpression is still unknown; interestingly, recent papers demonstrate that α 1 AR subtypes could dimerize. Thus, in the human urinary bladder it may be suggested a potential level of α 1 AR complexity that could have an impact on drug development.