This study was designed to further discriminate alpha(1)-adrenoceptor
subtypes in rat aorta and prostate using functional experiments. Respo
nses induced by phenylephrine were equilibrated in both tissues. The p
A(2) values and slope factors of several alpha(1)-antagonists were ass
essed using concentration-response curves. The antagonists used were p
razosin, WB-4101, 5-methylurapidil (5-MU), HV-723, and tamsulosin. In
addition, the effects of chloroethylclonidine (CEC) and nifedipine on
phenylephrine-induced contractions were investigated. A high pA(2) val
ue for prazosin was observed in both tissues (aorta 9.84, prostate 9.1
9) and the ranking of each drug's pA(2) value is as follows, tamsulosi
n > prazosin > WB-4101 > HV-723 > 5-MU in the aorta, and tamsulosin >
prazosin > 5-MU > WB-4101 = HV-723 in the prostate. A significant diff
erence between the pA(2) value of each drug except for tamsulosin in t
he aorta and in prostate was observed (p < 0.01). Inhibition of contra
ction by pretreatment with CEC was 83.9 +/- 2.42% in the aorta, and 6.
17 +/- 0.94% in the prostate. On the other hand, inhibition of maximal
response by pretreatment with nifedipine (l mu mol/l) was 35.1 +/- 2.
2% in the aorta and 24.5 +/- 3.1% in the prostate. A good correlation
between these PA(2) values and pK(i) values for recombinant human alph
a(1b)-adrenoceptor expressed in CHO cells (aorta) and alpha(1a)-sublyp
es of CEC pretreated rat hippocampus (prostate) were observed. In conc
lusion, these results suggest that: (1) the contraction of these two t
issues is mediated by alpha(1H)-adrenoceptor with a high affinity for
prazosin; (2) alpha(1H)-adrenoceptors correspond to alpha(1b)-(aorta)
and alpha(1a)-subtypes (prostate), and (3) each alpha(1)-adrenoceptor
subtype in the aorta and prostate may be alpha(1b)-(aorta) and alpha(1
a)-subtypes (prostate), respectively.