α₁-Adrenoceptors in the Guinea Pig Thoracic Aorta

抄録

In the present study, we tried to determine whichα₁-adrenoceptor subtypes are involvedin the guinea pig thoracic aorta by using in vitro functional analysis. In first, we tried toestimate the ρA₂ values of some key α₁-adrenoceptor antagonists (prazosin, 5-methylurapidil, WB4101, BMY7378 and tamsulosin) against responses to norepinephrine in thethoracic aorta of guinea pigs. The concentration-response curves of norepinephrine wererightward shifted by the presence of prazosin, 5-methylurapidil, WB4101, BMY7378 and tamsulosin. The ρA₂ values for these antagonists against norepinephrine were 7.83, 7.78, 8.20, 5.73 and 9.57, respectively. In second, we tried to compare the estimated ρA₂ values obtained in the present study with reported ρKi and ρpA₂ values for cloned and native α₁-adrenoceptor subtypes. In rabbit mesenteric artery, trigone, urethra, prostate and human lower urinary tract which were proposed to contain the putative α_1L-adenoceptor, weobtained the good correlation for the ρA₂ values reported in these tissues with ρA₂ values estimated in guinea pig thoracic aorta. Moreover, regression lines were close to the line of identity. These results suggest that the α₁-adenoceptors mediating contraction of guineapig thoracic aorta are similar pharmacologically to the putative α_1L-adenoceptor subtype inrabbit mesenteric artery, trigone, urethra, prostate and human lower urinary tract. As afinal point, guinea pig thoracic aorta may be able to use as a tool to develop the new α₁-adrenoceptor antagonist which is therapeutically advantageous in the treatment of urinarytract obstruction (e.g., in benign prostatic hyperplasia).