The ter (teratoma) gene causes germ cell deficiency and a high incidence of congenital testicular teratomas derived from primordial germ cells in 129/Sv‐ter strain mice. Ovarian teratomas in LTXBJ mice originate from ovarian parthenotes. In order to study the function of the ter gene in germ cell development and teratocarcinogenesis, we examined the influence of a foreign genetic background on the ter action by introducing the ter gene of 129/Sv‐ter strain mice into C57BL/6J, LTXBJ and C3H/HeJ genetic backgrounds by the backcross method and by thus establishing B6‐ter, LTXBJ‐ter and C3H‐ter ter congenic strains, respectively. Histological analysis showed that germ cell deficiency occurred in both sexes of the ter mutants, through the fetal stages to adulthood, but that congenital testicular teratocarcinogenesis did not occur after the fifth backcross generation. The ter/ter gonads were smaller than normal (+/+ or +/ter). Experimental testicular teratomas never developed from intratesticular grafts of B6‐ter genital ridges. LTXBJ‐ter/ter females had no ovarian teratomas. It is concluded that the ter gene is solely responsible for germ cell deficiency, but not testicular teratocarcinogenesis, in ter congenic strains having background genes other than 129/Sv‐ter and that the ter gene is not involved in ovarian teratocarcinogenesis.
Kaolin induced a clear and reproducible writhing reaction when intraperitoneally injected into mice. A simultaneous injection (i.p.) of soybean trypsin inhibitor (SBTI) significantly suppressed the kaolin-induced writhing reaction. This writhing reaction was markedly potentiated by a simultaneous injection (i.p.) of captopril. In an in vitro experiment kaolin caused kinin-release in mouse plasma, possibly through the activation of prekallikrein. This activation of plasma prekallikrein and kinin-release were inhibited in the presence of SBTI. Some non-steroidal anti-inflammatory agents inhibited the kaolin-induced writhing reaction dose-dependently. These results suggest that kaolin-induced writhing reaction may be caused by the released bradykinin through activation of the plasma kallikrein-kinin system. This model is a novel and simple tool for assessment of analgesic agents.
The mode of action of (+/-)-2-[p-[(2-methylallyl)amino]phenyl]propionic acid (EB-382) was studied in terms of its antiinflammatory effect. EB-382 displayed a more potent inhibitory effect than that of ibuprofen on carrageenin-induced paw edema in rats, and its inhibitory action was unaffected by adrenalectomy. EB-382 had a less potent inhibitory effect than that of ibuprofen on the prostaglandin E2 biosynthesis of 3T6 mouse fibroblast cells. EB-382 displayed a much more potent inhibitory effect than that of ibuprofen on carrageenin-induced pleurisy in rats. EB-382 exhibited a dose-dependent and significant inhibitory effect on the bradykinin and prostaglandin contents released into the pleural cavity in rat pleurisy induced by carrageenin, and its potency was much higher than that of ibuprofen. EB-382 strongly inhibited the leukocyte emigration into the pleural cavity, and its potency was almost equal to that of indomethacin. EB-382 did not affect the kinin-forming enzyme and kininase activities of rat plasma in vitro. The above results suggest that the antiinflammatory effect of EB-382 was probably due to inhibition of the production of bradykinin and prostaglandins derived from emigrating leukocytes in the local inflamed tissue besides a weak inhibitory effect on prostaglandin biosynthesis.
The analgesic mechanism of (+/-)-2-[p-[(2-methylallyl)amino]phenyl]propionic acid (EB-382), a new non-steroidal antiinflammatory agent, was studied. EB-382 exerted a potent analgesic effect on yeast-induced hyperalgesia in rats and bradykinin-induced writhing in mice, and its potency was superior to that of ibuprofen. EB-382 had a comparatively weak inhibitory effect on the prostaglandin E2 production from arachidonic acid in sheep seminal vesicle microsomal fraction in vitro. EB-382 exhibited a dose-dependent inhibitory effect on the phospholipase A2 activity in 3T3 mouse fibroblast cells with a different mechanism from steroidal agents, although indomethacin and ibuprofen did not reveal any significant inhibition. EB-382 did not affect the bradykinin-induced contraction of isolated rat uterus. Intracisternal injection of EB-382 did not affect the acetic acid-induced writhing response in mice. From these results, it is suggested that the analgesic effect of EB-382 in inflammation is exerted through its direct peripheral action, and inhibition of prostaglandin biosynthesis via phospholipase A2, rather than cyclooxygenase.
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