Alpha1 adrenoceptor subtypes in human urinary bladder: sex and regional comparison.
A detailed study of the presence of alpha1 AR binding sites and alpha1 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 alpha1 AR proteins were detectable in each bladder area. In both sexes, the detrusor and the neck expressed similar levels of alpha1 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 alpha1ARs 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 alpha1 AR subtype. The men detrusor expressed alpha1a and alpha1d 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 alpha1 AR subtype targeting arouses much interest, as evidence indicates that there are differences in signalling pathways among the subtypes. Furthermore, the significance of the alpha1 ARs coexpression is still unknown; interestingly, recent papers demonstrate that alpha1 AR subtypes could dimerize. Thus, in the human urinary bladder it may be suggested a potential level of alpha1 AR complexity that could have an impact on drug development.
Sigala
Sandra
S
Section of Pharmacology, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, V.le Europa 11, 25123 Brescia, Italy. sigala@med.unibs.it
Peroni
Angelo
A
Mirabella
Giuseppe
G
Fornari
Sara
S
Palazzolo
Francesca
F
Pezzotti
Giuseppe
G
Simeone
Claudio
C
Cunico
Sergio Cosciani
SC
Spano
PierFranco
P
D000368:Aged; D001665:Binding Sites; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D001743:Urinary Bladder / Q000378:metabolism*
D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1