Biomedical subjects

H Kogo

Publications and source records attributed to H Kogo.

At least 55 records · Page 3Linked to original sources

PubMed1998

17Beta-estradiol alters isoproterenol-induced relaxation in rat aortic rings.

Female Wistar rats were treated with 17beta-estradiol (E2) (10 microg, s.c.) or with sesame oil for 3 days. The relaxation induced by isoproterenol (10(-9)-3 x 10(-6) M) in aortae precontracted with norepinephrine was significantly suppressed in aortae from E2-treated rats compared with the relaxation in those from control rats. N(G)-Nitro-L-arginine, a nitric oxide synthase inhibitor, inhibited isoproterenol-induced relaxation in aortae from both E2-treated and control rats. Metyrapone, a cytochrome P-450 monooxygenase inhibitor, inhibited it in aortae from control rats, but metyrapone enhanced the maximum relaxation in aortae from E2-treated rats. These results suggest that E2 modulates isoproterenol-induced vasodilation through nitric oxide and cytochrome P-450-dependent metabolites.

Animals↗

PubMed1997

A regional variation of acetylcholine-induced relaxation in different segments of rat aorta.

The tension of the isolated thoracic aorta of the rat was measured isometrically to determine if there is a regional variation of the relaxation to acetylcholine (ACh). Endothelium-derived nitric oxide (NO)-dependent relaxation to ACh in the thoracic aorta precontracted with norepinephrine was significantly greater in the middle and distal segments than in the proximal segments. The relaxation to ACh was inhibited by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase. The relaxation to the NO donor sodium nitroprusside did not differ between the same three segments of the thoracic aorta. These results suggest that there are regional variations in the ACh-induced release of endothelium-derived NO in the rat thoracic aorta.

Acetylcholine↗

PubMed1997

Inhibitory effect of a new steroidal saponin, OSW-1, on ovarian functions in rats.

1. This study was undertaken to determine the effects of OSW-1 (3 beta, 16 beta, 17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)- (1-->3)-(2-O-acetyl-alpha-L-arabinopyranoside)) on the pituitary-ovarian system and the functions of aortic smooth muscle. 2. A single s.c. injection of OSW-1 (9 micrograms kg-1) on the morning of pro-oestrus inhibited the occurrence of the expected next pro-oestrus, whereas administration of OSW-1 at a dose of 4.5 micrograms kg-1 did not affect the oestrous cycle. OSW-1 treatment on the day of dioestrus-1 did not affect the oestrous cycle. 3. At doses of 4.5 and 9 micrograms kg-1 OSW-1, the serum oestradiol (E2) levels at the expected next pro-oestrus were significantly lower than in control (pro-oestrus). The serum luteinizing hormone (LH) levels 4 days after 9 micrograms kg-1 OSW-1 treatment were also markedly lower than those of control. OSW-1 (4.5 micrograms kg-1) did not affect the levels of inhibin, progesterone and gonadotrophins on the same day. 4. OSW-1 did not inhibit the preovulatory LH surge which occurs on the afternoon of pro-oestrus day. 5. The expression of mRNA coding for the cholesterol side chain cleavage cytochrome P-450 (p450scc), an ovarian steroidal limiting enzyme, was suppressed at 24 and 96 h after OSW-1 treatment. 6. Administration of OSW-1 (9 micrograms kg-1) tended to reduce the relaxation of isolated thoracic aorta ring preparations induced by acetylcholine, while there was no difference in the relaxation induced by sodium nitroprusside. 7. Our results show that OSW-1 inhibits ovarian E2 secretion and that the decrease in E2 secretion may contribute to its effects on the oestrous cycle and the sensitivity of the thoracic aorta to relaxation. The decrease in the levels of ovarian steroids induced by OSW-1 may be due to its direct inhibitory action on the gene expression of the steroidal enzyme and on the proliferation of granulosa cells in the ovary.

Animals↗

PubMed1997

Influence of OSW-1 [3 beta,16 beta,17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1--> 3)-(2-O-acetyl-alpha-L-arabinopyranoside)], a steroidal saponin, on endothelium dependent relaxation caused by acetylcholine in rat aorta.

The tension of isolated ring preparation of the aorta from rats was measured isometrically to study the influence of OSW-1 [3 beta,16 beta,17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1 right arrow 3)-(2-O-acetyl-alpha-L-arabinopyranoside)], a steroidal saponin, on the endothelium dependent and independent relaxation caused by acetylcholin (ACh) and sodium nitroprusside (SNP), respectively. OSW-1 (10(-7) M), which has more than 100 times higher concentration for anti-tumor activity, had no influence on either the endothelium dependent or independent relaxation. OSW-1 (10(-6) M, 0.9 microgram/ml) slightly reduced the endothelium dependent relaxation caused by ACh but did not affect the SNP-induced relaxation. In contrast to OSW-1, 1 mg/ml of saponin significantly suppressed the ACh-induced relaxation and shifted the dose-relaxation curve for SNP to the right. OSW-1 (10(-7) and 10(-6) M) did not affect the norepinephrine-induced contraction but 1 mg/ml of saponin significantly attenuated it. The results suggest that though the higher concentration of OSW-1 shows weaker influence on the endothelium function compared with saponin, OSW-1 at an anti-tumor dose has no influence on either endothelium or smooth muscle function.

Acetylcholine↗

PubMed1997

Acetylcholine-induced relaxation of rat aorta is greatest during estrus in the sexual cycle.

Acetylcholine (ACh)-induced relaxation in the aortae precontracted with norepinephrine was significantly enhanced in the aortae from estrus (E) rats, compared with that in those from metestrus (D-1), diestrus (D-2) and proestrus (PE) rats. NG-Nitro-L-arginine methyl ester (L-NAME) inhibited the endothelium-dependent relaxation in E rats. These results suggest that there is a difference in ACh-induced relaxation of the thoracic aorta during the sexual cycle of rats, and the relaxation is greatest in E of the sexual cycle; this may be due to a difference in nitric oxide synthesis in the endothelium in the sexual cycle.

Acetylcholine↗

PubMed1996

Altered intracellular Ca2+ regulation in pancreatic acinar cells from acute streptozotocin-induced diabetic rats.

We investigated intracellular Ca2+ regulation in pancreatic acinar cells from rats with diabetes induced by a single injection of streptozotocin (80 mg/kg). Experiments were performed 2 days and 7 days after the injection of streptozotocin. The density of muscarinic receptors, measured by [3H]N-methyl scopolamine binding, was unchanged in 2-day-diabetic rats, but was significantly increased in 7-day-diabetic rats. The percentage of high affinity receptors (RH) and low affinity receptors (RL) determined from the competitive curves with [3H]N-methyl scopolamine and carbachol was not change in 2-day-diabetic rats compared to controls, whereas 7-day-diabetic rats showed a decrease in %RH and an increase in %RL. The carbachol-evoked initial peak of intracellular Ca2+ concentration ([Ca2+]i) was increased in 2-day-diabetic rats and decreased in 7-day-diabetic rats, compared to controls. In the carbachol-induced sustained phase in [Ca2+]i, the response in 7-day-diabetic rats was significantly decreased; however, there was no difference between controls and 2-day-diabetic rats. Carbachol (100 microM)-induced [3H]inositol 1,3,4-trisphosphate generation was significantly lower in diabetic rats than in the controls. The addition of inositol 1,4,5-trisphosphate (1,4,5-IP3) significantly increased 45Ca2+ release from saponin-permeabilized cells in 2-day-diabetic rats, but did not do so in 7-day-diabetic rats. Ca2+ refilling into the intracellular stores, determined by second cholecystokinin-8 (10 nM) stimulation after 10 microM carbachol stimulation, was increased in 2-day-diabetic rats and decreased in 7-day-diabetic rats. These observations indicate that the alterations in intracellular Ca2+ regulation accompanied by changes in transmembrane signaling occur in the earlier stage of the diabetic state. The findings also suggest that the increase in the carbachol-evoked [Ca2+]i peak in 2-day-diabetic rats is related predominantly to the higher sensitivity of 1,4,5-IP3-sensitive Ca2+ stores and the increase in the capacity of Ca2+ refilling in these animals, whereas the reduction in the [Ca2+]i peak in 7-day-diabetic rats appears to be related to the essential decrease in receptor-mediated 1,4,5-IP3 generation and the decrease in Ca2+ refilling capacity.

Acute Disease↗

PubMed1996

Comparison of endothelium-derived relaxing factor activity between nonpregnant and pregnant rats.

The tension of isolated ring preparation of aorta from nonpregnant and pregnant rats was measured isometrically to study the effect of pregnancy on endothelium-derived relaxing factor activity. Contraction in response to norepinephrine and potassium chloride was greater in aortae from nonpregnant rats than in those from pregnant rats. The endothelium-dependent relaxation that was caused by acetylcholine (10(-10)-3 x 10(-9) M) in aortae precontracted with norepinephrine was significantly enhanced in aortae from pregnant rats compared with the relaxation in those from nonpregnant rats. NG-nitro-L-arginine methyl ester (L-NAME) inhibited the endothelium-dependent relaxation in both aorta from pregnant and nonpregnant rats. L-Arginine reversed the inhibition of L-NAME. Those results suggest that the enhanced endothelium-derived relaxing factor activity in rats aortae is associated with pregnancy.

Ammonium Chloride↗

PubMed1995

Characterization of gonadotropin-releasing hormone (GnRH)-immunoreactive protein in the rat pineal gland.

The aim of the present study was to characterize GnRH-like substance(s) in the rat pineal gland using a monoclonal antibody, LRH13, as a probe. The epitope of LRH13 is between 2nd and 5th amino acid residues of the mammalian GnRH, and its immunological characters were previously defined by us. LRH13 could show strong immunological signal on the rat pineal gland. Immunoblot after SDS-PAGE of the pineal gland preparations showed a LRH13 immunoreactive band with apparent mol wt 52 kilo-Dalton (kD), which is much bigger than that of hypothalamic GnRH precursor (10 kD). The 52 kD protein, however, was detected from insoluble fraction of the pineal homogenate and liberated from the fraction by Triton X-100 (2%) treatment. On the other hand, NaCl (140 mM and 500 mM) or EDTA (10 mM) treatment failed to liberate. Two-dimensional gel electrophoresis showed that the 52 kD protein is a mixture of two proteins with different isoelectric points (pI approximately 6.8 and 7.0). Both proteins showed identical patterns of peptide mapping by V8 protease digestion, and they might be originated from the same peptide. These results suggest that the rat pineal GnRH-immunoreactive substance has a unique property as a membrane associate protein.

Animals↗

PubMed1995

In situ detection of gonadotropin-releasing hormone (GnRH) receptor mRNA expression in the rat ovarian follicles.

To clarify the target cells of GnRH in the ovary, in vivo expression of ovarian GnRH receptor mRNA was examined histologically by in situ hybridization in immature rats treated with PMSG only or in combination with hCG. Strong hybridization signals were observed in the granulosa cells of atretic follicles. However, no significant signals were found in the granulosa cells of healthy small, preantral, or early antral follicles. Healthy Graafian and preovulatory follicles also showed intense signals in their mural granulosa cells, but no signals were detected in the cumulus oophorus cells. Corpora lutea showed only weak signals, but luteinizing follicles probably after atresia exhibited signals of moderate intensity in their luteinized and remaining granulosa cells. No signals were detected in the theca cells and oocytes in all the follicles. Interstitial cells sometimes exhibited hybridization signals of moderate intensity, when the cells were eosinophilic. Pretreatment with different combinations of gonadotropins yielded different ovarian histology, but this had no influence on the localization of hybridization signals. These results, showing that the authentic GnRH receptor mRNA was expressed in a certain cell population in the rat ovary, suggest that the receptor is involved in the control of various ovarian functions including follicular development, atresia, ovulation, and luteinization after ovulation and follicular atresia.

Animals↗

PubMed1995

Enhancing and inhibitory effects of nitric oxide on superoxide anion generation in human polymorphonuclear leukocytes.

1. The effects of sodium nitroprusside (SNP, a nitric oxide donor) and authentic nitric oxide (NO) on superoxide anion (O2-) generation were investigated in human polymorphonuclear leukocytes (PMNs). 2. Neither SNP (10 nM to 10 microM) nor NO (40 nM to 40 microM) alone induced O2- generation or change of intracellular Ca2+ concentration ([Ca2+]i) in human PMNs. 3. Pretreatment with SNP or NO at the concentrations used (SNP, 10 nM to 10 microM: NO, 40 nM to 40 microM) showed a biphasic concentration-dependent effect on O2- generation induced by f-methionyl-leucyl-phenylalanine (FMLP). Low concentrations of SNP (10 nM to 100 nM) and NO (400 nM) did not affect either basal cyclic GMP levels or cyclic GMP levels stimulated by FMLP, but enhanced FMLP-induced O2- generation and [Ca2+]i elevation. On the other hand, high concentrations of SNP (10 microM) and NO (40 microM) alone elevated cyclic GMP levels and inhibited FMLP-induced O2- generation and [Ca2+]i elevation. 4. 8-Bromo-cyclic GMP (8-Br-cyclic GMP) at concentrations ranging from 1 microM to 1 mM did not induce O2- generation on its own and had little effect on FMLP-induced O2- generation and [Ca2+]i elevation. 5. Addition of a high concentration of NO (40 microM) decreased authentic O2- formation by pyrogallol in a cell-free system, but a low concentration of NO (400 nM) had no effect on this. On the other hand, addition of SNP in the concentration-ranges used had no effect on authentic O2- formation by pyrogallol. 6. In this study, we have shown that SNP and NO have dual effects (enhancement and inhibition) on 02- generation induced by FMLP in human peripheral PMNs. The results suggest that the enhancement observed with SNP and NO at low concentrations is not mediated by activation of the guanylate cyclase-cyclic GMP pathway. The suppressive effect of SNP and NO at higher concentrations is mediated by the NO-induced O2--scavenging effect and activation of the guanylate cyclase-cyclic GMP pathway.

Calcium↗

PubMed1993

A role of prostaglandin in the secretion of inhibin and oestradiol-17 beta in equine chorionic gonadotrophin-primed rats.

The role of prostaglandins in the secretion of inhibin and oestradiol-17 beta was examined in immature female rats treated with equine chorionic gonadotrophin. Administration of prostaglandin (PG) F2 alpha to animals whose serum and ovarian levels of inhibin and oestradiol-17 beta had been suppressed by indomethacin given 24 h after equine chorionic gonadotrophin prevented the inhibition or restored the levels to normal. Initiation of PGF2 alpha replacement immediately after treatment with indomethacin was more effective. The results are consistent with the hypothesis that PGs play a regulatory role in the synthesis and secretion of inhibin and oestradiol-17 beta by the rat ovary.

Animals↗

PubMed1993

Inhibition by indomethacin of the already accelerated secretion of inhibin and estradiol in equine chorionic gonadotropin-primed immature female rats.

In immature female rats, the secretion of ovarian inhibin and estradiol is greatly accelerated by equine chorionic gonadotropin (eCG) treatment. The present study has been carried out to determine whether or not the levels of the two hormones are inhibited by a single s.c.-injection of indomethacin (INDO) 24 h after eCG administration. The levels of ovarian hormones and gonadotropins were measured by double-antibody radioimmunoassay using 125I-labeled radioligands. The serum levels of inhibin and estradiol were considerably inhibited within 24 and 12 h, respectively, after INDO injection. In addition, the serum levels of follicle-stimulating hormone (FSH) after INDO injection remained lower than the basal levels before eCG treatment. The luteinizing hormone (LH) levels were significantly reduced within 12 h after INDO treatment. The results demonstrate that the levels of inhibin and estradiol, even in the situation where the production of both hormones is already accelerated by eCG pretreatment, are suppressed by an inhibitor of prostaglandin (PG) synthesis, suggesting that locally produced PGs may play a role in the regulation of the production of both hormones in the ovary.

Animals↗

PubMed1993

A comparison of the effects of estradiol and 2- and 4-hydroxyestradiol on uterine ornithine decarboxylase activity in immature rats.

Effects of estradiol (E2) and catechol-estrogens (CEs: 2-OHE2 and 4-OHE2) on uterine ornithine decarboxylase (ODC) activity have been compared in immature rats. The intensity of their actions by s.c. (1 microgram) and intrauterine right-horn (i.u., 25 ng) injection was in the order of: 4-OHE2 > or = E2 > 2-OHE2. Although i.u. -injection of E2 caused an increase in ODC activity in the left (intact)-horn, which was about 60% that of the right-horn, the effects by CEs were limited only to the right-horn. The results are consistent with the previous view about the order of the potency of 4-OHE2 and 2-OHE2 and also suggest that locally produced CEs may play a role in the physiological functions of the production site.

Animals↗

PubMed1992

Indomethacin inhibits the secretion of inhibin and oestradiol-17 beta stimulated by pregnant mare serum gonadotrophin in the immature female rat.

The involvement of prostaglandins (PGs) in the regulation of inhibin and oestradiol-17 beta secretion from the ovary was studied by determining the effects of indomethacin and/or pregnant mare serum gonadotrophin (PMSG) on the levels of ovarian hormones in immature female rats. An increase in serum and ovarian levels of inhibin and oestradiol-17 beta was observed with a reciprocal reduction in serum follicle-stimulating hormone (FSH) levels from within 26 to 50 h after a single injection of 5 IU PMSG (s.c.) when the rats were 26 days of age. Administration of indomethacin to suppress PGs synthesis, simultaneously with PMSG, resulted in a substantial reduction in the levels of ovarian PGF2 alpha and serum inhibin and oestradiol-17 beta, which were both enhanced by PMSG treatment, 24 h after treatment with drugs. Indomethacin also reduced the basal serum level of inhibin. In the indomethacin-treated animals, the serum level of FSH was significantly increased regardless of the treatment with PMSG, indicating that the negative feedback regulation between FSH and inhibin is operating in these animals. These results demonstrate the inhibitory effects of indomethacin on PMSG-enhanced inhibin and oestradiol-17 beta production, suggesting that PGs play a regulatory role in the secretion of inhibin and oestradiol-17 beta from the gonadotrophin-stimulated ovary.

Animals↗

PubMed1992

Inhibitory and stimulatory actions of danazol in rat ovarian and uterine tissues.

We examined whether danazol has a direct action on ovarian steroid secretion and/or uterine prostaglandin (PG) F2 alpha catabolic activity in immature rats in which the first ovulation was induced and in adult ovariectomized rats. The preovulatory surge of estradiol and progesterone was markedly suppressed together with that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by danazol administration under conditions that blocked the first ovulation. Uterine weight and PGF2 alpha catabolic activity enhanced by endogenous estrogen were greatly decreased by danazol treatment at a dose that did not block the first ovulation in immature rats. When danazol (30 mg) was given s.c. once daily for 2 days to ovariectomized rats, the uterine weight and PGF2 alpha catabolic activity per uterus were clearly increased, and the compensatory increase in FSH levels as a result of castration was not influenced, although the compensatory increase in LH levels was inhibited. These results demonstrate that danazol has a direct action on the ovary and uterus, and give further support to the view put forward in our previous paper that these actions of danazol may contribute to its therapeutic effects.

Administration, Oral↗

PubMed1992

Agonistic-antagonistic actions of clomiphene citrate on PGF2 alpha fluctuations in ovariectomized rat uterus.

Effects of clomiphene and/or estrogen on uterine prostaglandin (PG) F2 alpha fluctuations in ovariectomized rats were examined. Uterine PGF2 alpha fluctuations were measured at the indicated times after injection of clomiphene and/or estradiol. Antiestrogenic effects of clomiphene on urine weight and PGF2 alpha levels were observed at 6 hr, and its effect on uterine 13,14-dihydro-15-keto-PGF2 alpha forming capacity was observed at 24 hr. At 48 and 72 hr, additive effects were recognized in all parameters. These results indicate that clomiphene possesses agonistic-antagonistic actions on the PGF2 alpha fluctuations in the uterus.

Animals↗

PubMed1991

Inhibition of the first ovulation and ovarian prostaglandin F2 alpha metabolism by danazol in rats.

The present study was conducted to investigate the mode of action of danazol by monitoring the first ovulation, serum luteinizing hormone (LH) levels and ovarian prostaglandin (PG) F2 alpha metabolism in pregnant mare serum gonadotropin (PMSG)-primed immature female rats. When danazol (750 mg/kg) was given p.o. once a day for 5 days (day 24-28), the occurrence of the first ovulation, the increase in capacity to form 13,14-dihydro-PGF2 alpha and PGF2 alpha levels induced by PMSG (5 IU) injected on day 26 were clearly inhibited on day 29. Danazol also markedly suppressed the LH surge occurring on day 28. Although the danazol-induced blockage of ovulation was restored by injection of human chorionic gonadotropin, the number of oocytes was significantly decreased as compared with that of controls. The present data indicate that the inhibitory actions of danazol on ovulation and ovarian PGF2 alpha metabolism may occur via some direct effects on the ovary in addition to the suppression of gonadotropin release from the pituitary gland.

Animals↗

PubMed1991

The effects of ovarian steroids in controlling rat uterine prostaglandin F2-alpha during the peri-implantation period.

Rats with delayed implantation, induced by ovariectomy or hypophysectomy, as well as those with normal pregnancy were used to examine the changes in uterine prostaglandin F2 alpha (PGF2 alpha) associated with implantation. In normal pregnant rats, while maximal uterine production of PGF2 alpha was found at 09:00, maximal catabolic enzyme activity (CEA) was seen at 17:00 of day 4. Uterine content of PGF2 alpha was high at 17:00 of day 4, but decreased by 80% within the next 24 h. There was no change in PGF2 alpha production during the first 6 h after injection of estradiol to hypophysectomized animals. There was, however, a dramatic decrease in production within the next 6 h. In contrast, CEA was not different in animals treated with estrogen than in those receiving only progesterone. In ovariectomized animals, uterine PGF2 alpha production also was lowered by estrogen but in these animals CEA was significantly elevated 18 h after injection of estradiol. Estrogen caused a greater increase in PGF2 alpha content in the hypophysectomized, compared to the ovariectomized, rats. The results are consistent with the view that ovarian steroids play an important role in controlling the changes in uterine PGF2 alpha around the time of implantation in rat.

Animals↗