[3H]bunazosin, a novel selective radioligand of alpha 1 adrenoceptors in human prostates.
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.
Yamada
S
S
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Suzuki
M
M
Matsuoka
Y
Y
Kato
Y
Y
Kimura
R
R
Maruyama
M
M
Kawabe
K
K
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008297:Male; D011224:Prazosin / Q000378:metabolism; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011799:Quinazolines / Q000378:metabolism*; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; C018176:bunazosin; D011224:Prazosin