Discrimination of alpha1-adrenoceptor subtypes in rat aorta and prostate.
This study was designed to further discriminate alpha1-adrenoceptor subtypes in rat aorta and prostate using functional experiments. Responses induced by phenylephrine were equilibrated in both tissues. The pA2 values and slope factors of several alpha1-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 pA2 value for prazosin was observed in both tissues (aorta 9.84, prostate 9.19) and the ranking of each drug's pA2 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 pA2 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 micromol/l) was 35.1 +/- 2.2% in the aorta and 24.5 +/- 3.1% in the prostate. A good correlation between these pA2 values and pKi values for recombinant human alpha1b-adrenoceptor expressed in CHO cells (aorta) and alpha1a-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 alpha1H-adrenoceptor with a high affinity for prazosin; (2) alpha1H-adrenoceptors correspond to alpha1b-(aorta) and alpha1a-subtypes (prostate), and (3) each alpha1-adrenoceptor subtype in the aorta and prostate may be alpha1b-(aorta) and alpha1a-subtypes (prostate), respectively.
Department of Pharmacology, Niigata College of Pharmacy, Niigata, Japan.
K
K
Maruyama
M
M
Suzuki
M
M
Tsuchiya
Y
Y
Makara
K
K
Hattori
T
T
Ohnuki
K
K
Watanabe
T
T
Nagatomo
D000097:Acetonitriles / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000097:Acetonitriles; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D014665:Vasodilator Agents; C058562:HV 723; C057446:5-methylurapidil; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D000077409:Tamsulosin; D009543:Nifedipine; D003000:Clonidine; D011224:Prazosin