花生四烯酸代谢产物对犬缓激肽诱导的伤害性反应的增强作用

Potentiation of bradykinin-induced nociceptive response by arachidonate metabolites in dogs.

作者信息

Hori Y, Katori M, Harada Y, Uchida Y, Tanaka K

出版信息

Eur J Pharmacol. 1986 Dec 2;132(1):47-52. doi: 10.1016/0014-2999(86)90007-5.

Abstract

Bradykinin was injected retrogradely into a branch of the splenic artery of lightly anesthetized dogs, and the reflex hypertensive response was used as an indicator of the nociception. The reflex hypertensive response to low doses of bradykinin (less than 1 nmol), but not to high doses (3-5 nmol), was markedly suppressed by infusion of indomethacin (0.54 mumol/min) into the splenic artery. During indomethacin infusion, the reflex hypertensive response to low doses of bradykinin was potentiated dose dependently by the following arachidonic acid metabolites (ED50): prostaglandin (PG)I2 (2.9 nmol) greater than or equal to PGH2 (4.4) greater than PGE2 (14) = thromboxane (TX)A2(15) greater than PGD2 (greater than 100). Leukotrienes B4, C4 and D4 showed practically no activity. This potentiating effect lasted up to 20 min after injection, particularly with PGE2. These results may not exclude the role of PGI2 as a major candidate for involvement in bradykinin-induced nociception, although a selective TX synthetase inhibitor (OKY-046) showed a weak analgesic effect (only 1/30 that of indomethacin).

摘要

将缓激肽逆行注入轻度麻醉犬的脾动脉分支，以反射性高血压反应作为伤害感受的指标。向脾动脉输注吲哚美辛（0.54 μmol/min）可显著抑制对低剂量缓激肽（小于1 nmol）而非高剂量（3 - 5 nmol）的反射性高血压反应。在输注吲哚美辛期间，对低剂量缓激肽的反射性高血压反应被下列花生四烯酸代谢产物剂量依赖性增强（半数有效剂量）：前列环素（PG）I2（2.9 nmol）≥前列腺素（PG）H2（4.4）＞前列腺素E2（14）=血栓素（TX）A2（15）＞前列腺素D2（＞100）。白三烯B4、C4和D4几乎无活性。这种增强作用在注射后可持续20分钟，尤其是前列腺素E2。这些结果虽不能排除前列环素作为参与缓激肽诱导的伤害感受的主要候选物质的作用，尽管一种选择性血栓素合成酶抑制剂（OKY - 046）显示出微弱的镇痛作用（仅为吲哚美辛的1/30）。