Characterization of subtype of alpha 1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed.
OBJECTIVE
To characterize the subtype of alpha 1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed.


METHODS
The potencies (pA2 values determined by Schild plot) of alpha 1-adrenoceptor-selective antagonists were determined by isolated vasoconstrictive experiment. The pKi values were determined by 125I-BE 2254 binding from the cloned alpha 1A-, alpha 1B-, and alpha 1D-adrenoceptor, stably expressed in human embryonic kidney (HEK) 293 cells.


RESULTS
The pA2 values for alpha 1A-adrenoceptor-selective antagonists, RS-17053, WB 4101, 5-methyl-urapidil, and the alpha 1D-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 alpha 1A-adrenoceptors (r = 0.97), but not for alpha 1B-adrenoceptors (r = 0.52) and alpha 1D-adrenoceptors (r = 0.04). The concentration-vasopressor response curve for norepinephrine was not affected by pretreatment with chloroethylclonidine (Chl) 50 mumol.L-1 for 30 min.


CONCLUSIONS
Only alpha 1A-adrenoceptors mediate the norepinephrine-induced vasopressor response in perfused rat mesenteric vascular bed.
Zhu
W Z
WZ
Institute of Vascular Medicine, Third Hospital, Beijing Medical University, China.
Zhang
Y Y
YY
Han
Q D
QD
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
C547713:ADRA1A protein, human; C547715:Adra1a protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D010879:Piperazines; C099495:RS 17053; D018340:Receptors, Adrenergic, alpha-1; D015016:Yohimbine; C053428:BMY 7378; D009638:Norepinephrine; D011224:Prazosin