Alpha-1 adrenoceptor subtypes (high, low) in human benign prostatic hypertrophy tissue according to the affinities for prazosin.
BACKGROUND
A novel classification of alpha-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH) tissue.


METHODS
Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies.


RESULTS
(1) Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29 +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd: 4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had different pKi values for the above two adrenoceptor subtypes. Scatchard analysis showed that alpha 1-high affinity binding site disappeared in the presence of 1 microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1 microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site of the two subtypes.


CONCLUSIONS
Human BPH tissue possesses both alpha 1H- and alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only the alpha 1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of alpha 1-adrenoceptors in prostatic tissue.
Takeda
M
M
Department of Urology, Niigata University, School of Medicine, Japan.
Hatano
A
A
Komeyama
T
T
Koizumi
T
T
Mizusawa
T
T
Kanai
T
T
Tomita
Y
Y
Maruyama
K
K
Nagatomo
T
T
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000368:Aged; D006801:Humans; D008297:Male; D011224:Prazosin / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification*
D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin