BIOLOGICAL-ACTIVITY OF METABOLITES OF PGD2 ON CANINE PROXIMAL COLON
BIOLOGICAL-ACTIVITY OF METABOLITES OF PGD2 ON CANINE PROXIMAL COLON
复制标题
DOI：
10.1152/ajpgi.1993.264.5.g886
复制
发表时间：
1993-05-01
影响因子：
--
通讯作者：
BETTI, PA
中科院分区：
文献类型：
--
作者：
RANGACHARI, PK;BETTI, PA
研究了犬结肠上皮对前列腺素D2 （PGD2）代谢产物的反应，并与亲本前列腺素D2诱导的反应进行了比较。PGD2的剂量-反应关系表现出三种不同的模式：1)在低浓度下，短路电流（I(sc)）呈剂量依赖性降低，然后在高浓度下呈剂量依赖性增加；2)剂量依赖性下降，即使在测试的最高浓度下也没有增加；3) I（sc）呈剂量依赖性增加，在任何浓度下均无下降。结肠对两种酶衍生代谢物13,14-二氢-15-酮- pgd2 （DK）和11β - pgf2alpha的反应不同。前者始终只产生剂量依赖性的I（sc）减少，而后者只引起剂量依赖性的增加。用11β - pgf2alpha预处理组织改变了对PGD2的反应，因此只注意到减少。相反，DK预处理导致PGD2仅引起I（sc）的增加。非酶衍生的PGJ2引起的反应与PGD2相似。用吲哚美辛预处理组织可消除对11β - pgf2α及其异构体pgf2α的反应，提示环加氧酶产物参与其中。然而，对PGE2的反应被放大。两种异构体之间存在交叉脱敏现象。对11β -PGF2alpha或PGF2alpha脱敏的组织对DK和PGE2均有反应；然而，对PGE2脱敏的组织对11β - pgf2alpha无反应。因此，犬结肠上皮不仅对PGD2有反应，而且对其衍生代谢物也有反应。动物对PGD2反应的差异可能源于受体水平的差异和/或这些代谢物产生的差异。
The responses of the canine colonic epithelium to the metabolites of prostaglandin D2 (PGD2) Were compared with those elicited by the parent prostanoid. Dose-response relations to PGD2 showed three distinct patterns: 1) a dose-dependent decrease in short-circuit current (I(sc)) at lower concentrations followed by a dose-dependent increase at higher concentrations; 2) dose-dependent decreases, with no increase even at the highest concentrations tested; and 3) dose-dependent increases in I(sc), with no decreases at any concentration. The colon responded differently to the two enzymatically derived metabolites 13,14-dihydro-15-keto-PGD2 (DK) and 11beta-PGF2alpha. The former consistently produced only dose-dependent decreases in I(sc), while the latter elicited only dose-dependent increases. Pretreatment of tissues with 11beta-PGF2alpha altered the responses to PGD2 such that only decreases were noted. Conversely, pretreatment with DK caused PGD2 to elicit only increases in I(sc). The nonenzymatically derived PGJ2 elicited responses comparable to those seen with PGD2. Pretreatment of tissues with indomethacin abolished responses to 11beta-PGF2alpha as well as its isomer, PGF2alpha, suggesting the involvement of a cyclooxygenase product. Responses to PGE2 were, however, amplified. Cross-desensitization was noted between the two isomers. Tissues desensitized to either 11beta-PGF2alpha or PGF2alpha, were responsive to DK as well as PGE2; however, tissues desensitized to PGE2 were unresponsive to 11beta-PGF2alpha. Thus the canine colonic epithelium responds not only to PGD2 but also to its derived metabolites. Variability in the response to PGD2 between animals could stem from differences at the receptor level and/or differential production of these metabolites.