Abstract
This study was designed to further discriminate α<sub>1</sub>-adrenoceptor subtypes in rat aorta and prostate using functional experiments. Responses induced by phenylephrine were equilibrated in both tissues. The pA<sub>2</sub> values and slope factors of several α<sub>1</sub>-antagonists were assessed using concentration-response curves. The antagonists used were prazosin, 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<sub>2</sub> value for prazosin was observed in both tissues (aorta 9.84, prostate 9.19) and the ranking of each drug’s pA<sub>2</sub> value is as follows: tamsulosin > prazosin > WB-4101 > HV-723 > 5-MU in the aorta, and tamsulosin > prazosin > 5-MU > WB-4101 = HV-723 in the prostate. A significant difference between the pA<sub>2</sub> value of each drug except for tamsulosin in the aorta and in prostate was observed (p < 0.01). Inhibition of contraction 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 (1 µmol/l) was 35.1 ± 2.2% in the aorta and 24.5 ± 3.1% in the prostate. A good correlation between these pA<sub>2</sub> values and pK<sub>i</sub> values for recombinant human α<sub>1b</sub>-adrenoceptor expressed in CHO cells (aorta) and α<sub>1a</sub>-subtypes of CEC pretreated rat hippocampus (prostate) were observed. In conclusion, these results suggest that: (1) the contraction of these two tissues is mediated by α<sub>1H</sub>-adrenoceptor with a high affinity for prazosin; (2) α<sub>1H</sub>-adrenoceptors correspond to α<sub>1b</sub>-(aorta) and α<sub>1a</sub>-subtypes (prostate), and (3) each α<sub>1</sub>-adrenoceptor subtype in the aorta and prostate may be α<sub>1b</sub>-(aorta) and α<sub>1a</sub>-subtypes (prostate), respectively.
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