Localization of mRNA and receptor binding sites for the alpha 1a-adrenoceptor subtype in the rat, monkey and human urinary bladder and prostate.
OBJECTIVE
To localize the mRNAs and receptor binding sites for the alpha 1a/A, alpha 1b/B and alpha 1d/D- adrenoceptor (AR) subtypes in the rat, monkey and human urinary bladder and prostate.


METHODS
alpha 1-AR mRNAs were localized on slide mounted tissue sections by in situ hybridization using [35S]-labeled subtype specific oligonucleotide probes. alpha 1-AR receptor binding sites were localized on slide mounted tissue sections by competitive displacement of [3H]-prazosin using subtype selective ligands.


RESULTS
Only the alpha 1a-AR subtype mRNA was discernible by in situ hybridization. The alpha 1a-AR mRNA was localized in all smooth muscle areas of the rat, monkey and human urinary bladder and prostate. High levels of alpha 1a mRNA were detected in bladder dome and bladder base urothelium. Competitive displacement studies using the alpha 1A-AR selective ligand SNAP 5272 revealed that the alpha 1A-AR represented over 80% of the total alpha 1-AR in monkey bladder and prostate. In general, localization of the alpha 1A-AR corresponded to the alpha 1a-AR mRNA localization, that is, receptor protein was localized to smooth muscle areas of the bladder dome, trigone and base and prostate. One notable exception was the bladder urothelium, which contained high levels of alpha 1a-AR mRNA, but undetectable levels of alpha 1A-AR protein. The alpha 1a-AR mRNA appeared to be transcribed but not translated in bladder urothelium.


CONCLUSIONS
The alpha 1A-AR represents the major subtype in the smooth muscle of rat, monkey and human urinary systems. Selective alpha 1A-AR agents are therefore potentially useful in the treatment of multiple urinary smooth muscle related disorders.
Walden
P D
PD
Department of Urology, NYU Medical Center, New York, USA.
Durkin
M M
MM
Lepor
H
H
Wetzel
J M
JM
Gluchowski
C
C
Gustafson
E L
EL
D000818:Animals; D001665:Binding Sites; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D011467:Prostate / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D001743:Urinary Bladder / Q000737:chemistry*
D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1