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

摘要

A detailed study of the presence of alpha(1) AR binding sites and alpha(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 alpha(1) AR proteins were detectable in each bladder area. In both sexes, the detrusor and the neck expressed similar levels of alpha(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 alpha(1)ARs 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 alpha(1) AR subtype. The men detrusor expressed alpha(1a) and alpha(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 alpha(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 alpha(1) ARs coexpression is still unknown; interestingly, recent papers demonstrate that alpha(1) AR subtypes could dimerize. Thus, in the human urinary bladder it may be suggested a potential level of alpha(1) AR complexity that could have an impact on drug development.