Matsumoto K, Akimoto A, Shibata K, Obata T, Tsuda T, Tsuboshima M
Nihon Yakurigaku Zasshi. 1981 Oct;78(4):231-8.
In rats on day 20 of pregnancy, ONO-802 exerted a uterine contractile effect when 0.2 microgram/kg was given i.v. and also with an intrauterine administration of 0.5 ng, s.c. administration of 1 microgram/kg and vaginal administration of 10 microgram/kg. The contractile activity of ONO-802 was 100-1000 times more potent than that of PGE2 alpha and was long-acting. Intravenous PGE1 or PGE2 induced a transient contraction followed by inhibition of spontaneous uterine motility in nonpregnant rats and in those with an early pregnancy. In nonpregnant hamsters, a relaxation was seen. ONO-802, similar to PGF2 alpha, showed a contractile effect regardless of states of nonpregnancy and pregnancy, both rats and hamsters. IN rats, a contractile threshold dose of ONO-802 was similar from day 15 to day 21 of pregnancy. Oxytocin produced an acute decrease in this threshold dose on phentolamine or methysergide, but was inhibited by papaverine, dibutyryl cAMP, salbutamol and verapamil. These results suggest that uterine contraction induced by ONO-802 differs from the contractions induced by PGE1, PGE2, and oxytocin, that ONO-802 does not induce endogenous PGs, and that the effect of ONO-802 is not mediated by the autonomic nervous system.
在妊娠第20天的大鼠中,静脉注射0.2微克/千克的ONO - 802以及子宫内给予0.5纳克、皮下注射1微克/千克和阴道给予10微克/千克时,ONO - 802均发挥子宫收缩作用。ONO - 802的收缩活性比PGE2α强100 - 1000倍,且作用持久。静脉注射PGE1或PGE2可引起短暂收缩,随后抑制未孕大鼠和早孕大鼠的子宫自发运动。在未孕仓鼠中则出现松弛现象。ONO - 802与PGF2α相似,无论大鼠和仓鼠处于未孕还是妊娠状态,均表现出收缩作用。在大鼠中,妊娠第15天至第21天,ONO - 802的收缩阈剂量相似。催产素可使酚妥拉明或麦角新碱作用下的该阈剂量急剧降低,但可被罂粟碱、二丁酰cAMP、沙丁胺醇和维拉帕米抑制。这些结果表明,ONO - 802诱导的子宫收缩不同于PGE1、PGE2和催产素诱导的收缩,ONO - 802不诱导内源性PGs,且ONO - 802的作用不是由自主神经系统介导的。