Lefebvre R A, Burnstock G
Heymans Institute of Pharmacology, University of Ghent Medical School, Belgium.
Arch Int Pharmacodyn Ther. 1990 Jan-Feb;303:199-215.
The effect of adenosine triphosphate (ATP) and its analogues was studied in longitudinal muscle strips of the rat gastric fundus in order to characterize the purinoceptors involved. At resting tension, 10(-4) M ATP usually induced a small initial relaxation followed by a contraction; when tone was raised by administration of carbachol (10(-7) M), ATP (10(-4) M) induced a larger relaxation followed by a smaller rebound contraction. Both the contraction at resting tension and the rebound contraction were antagonized by indomethacin. With raised tone, both ATP and 2-methylthioATP induced concentration-dependent relaxations, followed by small rebound contractions, but the slope of the concentration-response curve was very shallow. alpha, beta-MethyleneATP and adenosine induced only concentration-dependent relaxations and the maximal effect was much more pronounced than that of ATP and 2-methyl-thioATP. The rank order of potency of the purines producing relaxation was 2-methylthioATP greater than alpha, beta-methyleneATP greater than ATP greater than adenosine. The relaxant effect of ATP (10(-4) M) at raised tone was clearly antagonized by both reactive blue 2 (10(-4) M) and desensitization to alpha, beta-methyleneATP. It is concluded that the contractile effect of ATP in the rat gastric fundus is due to stimulation of prostaglandin biosynthesis, but identification of the purinoceptor subtype mediating relaxation is problematic and it may differ from the P2x- and P2y-receptors, which are clearly distinguishable in a number of other tissues.
为了确定所涉及的嘌呤受体的特征，研究了三磷酸腺苷（ATP）及其类似物对大鼠胃底纵行肌条的作用。在静息张力下，10⁻⁴ M ATP通常先引起小的初始舒张，随后是收缩；当通过给予卡巴胆碱（10⁻⁷ M）提高肌张力时，ATP（10⁻⁴ M）引起更大的舒张，随后是较小的反弹性收缩。吲哚美辛可拮抗静息张力下的收缩和反弹性收缩。肌张力升高时，ATP和2-甲硫基ATP均引起浓度依赖性舒张，随后是小的反弹性收缩，但浓度-反应曲线的斜率非常平缓。α,β-亚甲基ATP和腺苷仅引起浓度依赖性舒张，且最大效应比ATP和2-甲硫基ATP更明显。产生舒张作用的嘌呤的效力顺序为：2-甲硫基ATP＞α,β-亚甲基ATP＞ATP＞腺苷。活性蓝2（10⁻⁴ M）和对α,β-亚甲基ATP脱敏均明显拮抗肌张力升高时ATP（10⁻⁴ M）的舒张作用。结论是，ATP在大鼠胃底的收缩作用是由于刺激前列腺素生物合成所致，但介导舒张的嘌呤受体亚型的鉴定存在问题，它可能不同于在许多其他组织中可明确区分的P2x和P2y受体。
