Characterization of subtype of alpha 1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed
Zhu, W.Z.; Zhang, Y.Y.; Han, Q.D.
Zhongguo Yao Li Xue Bao 20(2): 151-156
1999
ISSN/ISBN: 0253-9756 PMID: 10437163 Document Number: 502437
AIM: To characterize the subtype of alpha1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed. METHODS: The potencies (pA2 values determined by Schild plot) of alpha1-adrenoceptor-selective antagonists were determined by isolated vasoconstrictive experiment. The pKi values were determined by 125I-BE 2254 binding from the cloned alpha1A-, alpha1B-, and alpha1D-adrenoceptor, stably expressed in human embryonic kidney (HEK) 293 cells. RESULTS: The pA2 values for alpha1A-adrenoceptor-selective antagonists, RS-17053, WB 4101, 5-methyl-urapidil, and the alpha1D-adrenoceptor-selective antagonist, BMY 7378, were 8.98 +- 0.28, 9.16 +- 0.20, 8.69 +- 0.02, and 6.03 +- 0.26, respectively, with the slope not different from unity. The pA2 values of the above antagonists correlated well with the binding pKi values only for alpha1A-adrenoceptors (r = 0.97), but not for alpha1B-adrenoceptors (r = 0.52) and alpha1D-adrenoceptors (r = 0.04). The concentration-vasopressor responsecurve for norepinephrine was not affected by pretreatment with chloroethylclonidine (Chl) 50 mumol cntdot L-1 for 30 min. CONCLUSION: Only alpha1A-adrenoceptors mediate the norepinephrine-induced vasopressor response in perfused rat mesentric vascular bed.