| Abstract | The binding properties of a new radioligand, [3H]bunazosin, were studied in membranes of human prostates with benign prostatic hypertrophy (BPH). Specific binding of [3H]bunazosin was saturable, reversible, and of high affinity (Kd = 0.55 +/- 0.04 nM). The density of [3H]bunazosin binding sites (Bmax) was 676 +/- 33 fmol/mg. protein. [3H]Bunazosin rapidly associated with its binding sites in membranes of human prostates and reached steady state by 20 min. at 25C. The rate constants for association and dissociation of [3H]bunazosin binding were calculated to be 0.11 +/- 0.01/nM/min. and 0.05 +/- 0.02/min. (n = 4), respectively. Seven alpha 1 adrenoceptor antagonists competed with [3H]bunazosin for the binding sites in the rank order: R-(-)-YM-12617 greater than prazosin greater than SGB-1534 greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil. In parallel studies with [3H]bunazosin, the Kd and Bmax values for [3H]prazosin binding in human prostates were slightly lower. There was a similarity in the potency and rank order of seven alpha 1, adrenoceptor antagonists for the inhibition of [3H] bunazosin and [3H]prazosin binding in human prostates. The new [3H]bunazosin binding assay in human prostates is remarkable for its low degree of nonspecific binding as compared to [3H]prazosin, especially at high ligand concentrations. Thus, [3H]bunazosin may become a useful radioligand for the further analysis of the alph 1 adrenoceptor binding sites in human prostates. |
| Authors | S Yamada, M Suzuki, Y Matsuoka, Y Kato, R Kimura, M Maruyama, K Kawabe
(Affiliation: Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Japan.)
|
| Journal | The Journal of urology
(J Urol)
Vol. 146
Issue 3
Pg. 877-80
(Sep 1991)
ISSN: 0022-5347 UNITED STATES |
| PMID | 1714973
(Publication Type: Journal Article)
|
| Chemical References |
- Adrenergic alpha-Antagonists
- Quinazolines
- Receptors, Adrenergic, alpha
- Tritium
- Prazosin
- bunazosin
|
| Topics |
- Adrenergic alpha-Antagonists
(metabolism, pharmacology)
- Cell Membrane
(metabolism)
- Humans
- Male
- Prazosin
(metabolism)
- Prostate
(metabolism)
- Prostatic Hyperplasia
(metabolism)
- Quinazolines
(metabolism)
- Radioligand Assay
- Receptors, Adrenergic, alpha
(metabolism)
- Tritium
|
