Inhibitory effect of acemetacin, a prodrug of indomethacin, on prostaglandin E2 release from inflamed synovial tissue.
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Biomedical subjects
Publications and source records attributed to H Kogo.
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In order to examine a possible role of the pituitary gland and uterine tissue in the formation of 13,14-dihydroprostaglandin F2 alpha (13,14H2-PGF2 alpha) in rat ovary, hypophysectomized and hysterectomized rats were used. Gonadotropins stimulated the formation of 13,14H2-PGF2 alpha from prostaglandin F2 alpha (PGF2 alpha) and 13,14-dihydro-15-keto-PGF2 alpha (15KD-PGF2 alpha) in the ovarian homogenate of hypophysectomized and hysterectomized rats as well as in intact rats. Ovarian steroids, estradiol and progesterone, reduced the formation of 13,14H2-PGF2 alpha in the ovarian homogenate of intact rats. However, in hysterectomized and hypophysectomized rats, its formation was not affected by ovarian steroids. On the other hand, when pregnant mare serum gonadotropin (PMS) and estradiol were simultaneously administered to intact and hypophysectomized rats, the formation of 13,14H2-PGF2 alpha in the ovary showed a tendency to be increased as compared with that after treatment with PMS alone. These results not only suggest that the formation of 13,14H2-PGF2 alpha in rat ovary is regulated by gonadotropins and ovarian steroids, but also that uterine tissue may take part in the process of its formation.
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Effects of pregnant mare serum gonadotropin and human chorionic gonadotropin on the formation of 13,14-dihydroprostaglandin F2 alpha, a biologically active compound, were investigated in rat ovarian homogenate. The mass number of the compound, which was formed prostaglandin F2 alpha via 13,14-dihydro-15-ketoprostaglandin F2 alpha in rat ovarian homogenate but was not produced in rat homogenate, accorded with that of the authentic 13,14-dihydroprostaglandin F2 alpha by negative ion chemical ionization mass spectrometry. In the present experiment, the radioactivity of [3H]prostaglandin F2 alpha added to ovarian homogenate was decreased linearly and immediately until the incubation time of 10 min. The formation of 13,14-dihydroprostaglandin F2 alpha was increased up to 60 min. The formation of 13,14-dihydroprostaglandin F2 alpha from prostaglandin F2 alpha was markedly increased by pregnant mare serum gonadotropin and human chorionic gonadotropin. However, there was no additive or synergistic effect of these hormones. The formation of 13,14-dihydroprostaglandin F2 alpha from 13,14-dihydro-15-ketoprostaglandin F2 alpha weas also greatly stimulated by pregnant mare serum gonadotropin and human chorionic gonadotropin. The formation of 13,14-dihydro-15-ketoprostaglandin F2 alpha steeply declined until 24 h after treatment with human chorionic gonadotropin in pregnant mare serum gonadotropin-primed rats. In contrast, the formation of 13,14-dihydroprostaglandin F2 alpha was markedly increased until 24 h after human chorionic gonadotropin treatment, and the level was about 2.5-fold higher than that at 0 h, 48 h after injection of pregnant mare serum gonadotropin.
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We studied the influence of rat renal prostaglandin on the effect of vasopressin, in vivo. In water-loaded rats, vasopressin induced a dose-related increase in total urinary prostaglandin E and prostaglandin F excretion and a decrease in total urine output. Urine excretion, which peaked in water-loaded controls during the first 2 h after loading, was suppressed in vasopressin-treated rats, however, their urinary prostaglandin E excretion was markedly enhanced. This increase in urinary prostaglandin E was suppressed by the simultaneous administration of indomethacin, and the 3-6 h post-administration peak in urine output of vasopressin-treated rats was inhibited. In hypophysectomized rats, urine excretion increased gradually after surgery, however, urinary prostaglandin E excretion decreased. Based on our present findings, we suggest that prostaglandin E produced in the rat kidney modulate the renal response to vasopressin.
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Effects of pregnant mare serum gonadotropin (PMS) and estradiol on the formation of 13,14-dihydroprostaglandin F2 alpha (13,14H2-PGF2 alpha) from prostaglandin F2 alpha (PGF2 alpha) and 13,14-dihydro-15-ketoprostaglandin F2 alpha (15KD-PGF2 alpha) in the ovarian homogenate of rats were examined. PMS and estradiol were given to the rats (s.c.) on the first day of diestrus, and the ovaries were removed 24 hours after treatment with each hormone. PMS stimulated the formation of 13,14H2-PGF2 alpha from PGF2 alpha and 15KD-PGF2 alpha, and estradiol markedly inhibited the formation of 13,14H2-PGF2 alpha from PGF2 alpha and 15KD-PGF2 alpha. However, the formation of 15KD-PGF2 alpha from PGF2 alpha did not change with PMS and estradiol. These results indicate that 13,14H2-PGF2 alpha formed in rat ovary may play some important role in ovarian function and may be regulated by gonadotropins and ovarian steroids.
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Effects of gonadotropin and estrogen on the levels of prostaglandin (PG) in the rat ovary wer investigated. PGF content in rat ovary, as measured by radioimmunoassay, was slightly higher than that by bioassay using rat stomach fundus, although there was no statistically significant difference. PGE and PGF levels in rat ovary during the estrous cycle were lowest on the day of diestrus, PGE was of the highest level on the day of estrus, and PGF on the day of proestrus. Both PGE and PGF were increased 24 hours after treatment with pregnant mare serum gonadotropin on the first day of diestrus. PGE was increased about 2.5 fold and PGF about 2.3 fold. PGF was significantly increased 24 hours after treatment with estradiol on the first day of diestrus. These results suggest that gonadotropin may directly or indirectly regulate changes in ovarian PG content via actions of estrogen.
Effect of methylxanthines (theophylline, theobromine and caffeine) on urinary prostaglandin E (PGE) excretion in male rats was studied. Oral administration of xanthines significantly increased the urinary excretion of PGE. Dose-response studies showed that the maximal excretion of urinary PGE and water was obtained by administration of theophylline (50 mg/kg), where the increase in PGE was about 20 times that of the control. The excretion of urinary sodium, potassium and chloride was also markedly increased by xanthines, particularly, theophylline. Increases in urinary PGE excretion, urine volume and electrolytes excretion were inhibited by 10 mg/kg of indomethacin administered prior to theophylline. The increase of urinary PGE excretion after theophylline administration (50 mg/kg) preceded increases in water and sodium excretion. These results suggest that renal PGE mediates, at least in part, the diuretic effect of theophylline.
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The role of uterine tissue in the changes of rat ovarian prostaglandin (PG) content was investigated. PGE and PGF levels in rat ovary were decreased to about one-fourth of control levels by hysterectomy, when the contents were determined on the day of estrus 4 days after surgery. Both the PGE and PGF contents in diestrous ovary 10 to 14 days after hysterectomy tended to be decreased, as compared with those in intact control (diestrus), but not significant difference was observed. Administration of estradiol to hysterectomized rats on the day of diestrus increased neither PGE nor PGF levels. Also with the administration of pregnant mare serum gonadotropin, no increase in the PG contents was seen in the ovary of hysterectomized rats. The incorporation of 3H-arachidonic acid into the 3H-PGE and 3H-PGF fractions, expressed in terms of the organ, was much greater in the uterus than in the ovary. The incorporation of 3H-arachidonic acid into the 3H-PGE and 3H-PGF fractions in the ovary was higher on the day of estrus than on the day of diestrus. These results strongly suggest that the changes in the PG content in rat ovary may be regulated, at least in part, by uterine tissue.
The effect of methylxanthines (theophylline, theobromine, caffeine) on urinary prostaglandin E (PGE) excretion in rats was investigated. Male rats, weighing 270-300g only were used. Food was withdrawn 3 hr before the experiment and water intake was free during the test period. In saline or water loaded experiments, 0.9%, 9% NaCl solution or water containing each drug was administered orally in a volume of 2.5 ml/100g. The urinary PGE was measured by bioassay using rat stomach fundus strip. In rats loaded with isotonic saline, the urinary PGE excretion was increased by methylxanthines and the greatest effect was seen with theophylline. The effect of theophylline on PGE excretion was evident in non-loaded and isotonic saline-loaded rats. In particular, the percentages of PGE, sodium and chloride in the urine were remarkably increased, as compared with findings in the control. In non-loaded and isotonic saline-loaded rats, the urinary PGE excretion induced by theophylline correlated significantly with the sodium and chloride excretion. These results suggest the participation of renal PGE in the effects of theophylline on kidney function.
The catabolism in vitro of prostaglandin F2 alpha (PGF2 alpha) in rat ovarian homogenate was studied comparing with uterine homogenate. Two kinds of metabolite were recognized by incubation of PGF2 alpha with ovarian or uterine homogenate; 13, 14-dihydro-15-keto-PGF2 alpha (15KD-PGF2 alpha) and 13, 14-dihydro-PGF2 alpha (13, 14H2-PGF2 alpha) in ovarian homogenate and 15-keto-PGF2 alpha (15K-PGF2 alpha) and 15KD-PGF2 alpha in uterine homogenate. Incubation of 15KD-PGF2 alpha with ovarian homogenate resulted in the formation of 13, 14H2-PGF2 alpha but incubation with uterine homogenate did not produce 13, 14H2-PGF2 alpha. 13, 14H2-PGF2 alpha was in accord with Rf value of a compound formed by reduction of 15KD-PGF2 alpha with sodium borohydride.