Functional alpha1-adrenergic receptor subtypes in human right gastroepiploic artery.
OBJECTIVE
To study the functional alpha1-adrenergic receptor (alpha1-AR) subtypes in human right gastroepiploic artery (RGA).


METHODS
The effects of alpha2-AR, alpha1-AR, and alpha1-AR subtype selective antagonists on norepinephrine (NE)-induced vasoconstriction in isolated human RGA were observed by contractile function experiment.


RESULTS
Cumulative concentration-response curves for NE were competitively antagonized in RGA by alpha2-AR selective antagonist yohimbine (pA2 6.82+/-0.28, slope 1.12+/-0.40),alpha1-AR selective antagonist prazosin (pA2 9.77+/-0.22, slope 0.90+/-0.22),alpha1A-AR selective antagonists RS17053 (pA2 8.42+/-0.20, slope 0.93+/-0.20) and 5-MU (pA2 8.42+/-0.22, slope 0.88+/-0.18),alpha1D-AR selective antagonist BMY7378 (pA2 6.84+/-0.32, slope 1.05+/-0.17), and alpha1A-,alpha1B-AR selective antagonist WB4101 (pA2 8.88+/-0.20, slope 1.15+/-0.16). The correlation coefficients between these pA2 values of alpha1-AR selective antagonists with pKi values of which obtained from alpha1A-, alpha1B- and alpha1D-AR cloned cells are 0.95, 0.82, and 0.42. After the vessels were pretreated by chlorethylclonidine (CEC), an alpha1B- and alpha1D-AR irreversible alkylating agent, the pD2 values were changed from 5.9+/-0.5 to 5.6+/-0.6 and the maximal contraction was changed from (8.9+/-3.2) g to (8.0+/-3.2) g, respectively. The difference was not significant.


CONCLUSIONS
In human RGA, the contraction response is mainly mediated by alpha1-AR, of which alpha1A-AR plays an important role, whereas alpha1B- and alpha1D-AR are not involved in the contraction response.
Han
Jiang-Li
JL
Institute of Vascular Medicine, Third Hospital, Peking University, Beijing 100083, China. hanqd@bjumu.edu.cn
Zhang
You-Yi
YY
Lü
Zhi-Zhen
ZZ
Mao
Jie-Ming
JM
Chen
Ming-Zhe
MZ
Han
Qi-De
QD
D058668:Adrenergic alpha-1 Receptor Antagonists; D000328:Adult; D000368:Aged; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D024405:Gastroepiploic Artery / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1
C547713:ADRA1A protein, human; C547716:ADRA1B protein, human; C547719:ADRA1D protein, human; D058668:Adrenergic alpha-1 Receptor Antagonists; D004146:Dioxanes; D007211:Indoles; D010879:Piperazines; C099495:RS 17053; D018340:Receptors, Adrenergic, alpha-1; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C053428:BMY 7378