Biomedical subjects

Y Okatani

Publications and source records attributed to Y Okatani.

At least 19 recordsLinked to original sources

PubMed1998

Effect of estrogen on melatonin synthesis in female peripubertal rats.

Our objective was to evaluate the effect of estrogen on the synthesis of melatonin in female rats during the peripubertal period. The level of melatonin and of N-acetyl serotonin (NAS) and the activity of N-acetyltransferase (NAT) and of hydroxy-indole-O-methyltransferase (HIOMT) were determined in homogenates of pineal glands from peripubertal female Sprague-Dawley rats in the mid-dark during the daily light/dark cycle between 4 and 10 weeks of age. Ovariectomy was performed and daily administration of estradiol benzoate (E2B) was initiated at 6 weeks of age. A peak in the pineal level of melatonin and NAS and in NAT activity was observed in untreated (control) rats with intact ovaries at 6 weeks. Thereafter, HIOMT activity increased and remained unchanged. Ovariectomy at week 6 led to significant increases in the level of melatonin and of NAS and in NAT activity at week 8. At week 10, NAT activity was similar to that of control animals, but melatonin and NAS levels were slightly elevated. Ovariectomy did not affect HIOMT activity. The subcutaneous injection of a low dose (0.1 microg/day) of E2B suppressed the ovariectomy-induced elevation of levels of melatonin and NAS and of NAT activity, similar to that seen in rats with intact ovaries. A higher dose of E2B (1.0 microg/day) reduced the activity of NAT and HIOMT to values significantly below the control values. Results suggest that estrogen modulates the nocturnal synthesis of melatonin by the pineal gland in peripubertal female rats. The decline in melatonin synthesis during puberty may be related to an increase in the estrogen level. The inhibitory effect of estrogen in melatonin synthesis appeared to be mediated by the modulation of NAT activity.

Acetylserotonin O-Methyltransferase↗

PubMed1997

Nocturnal changes in pineal melatonin synthesis during puberty: relation to estrogen and progesterone levels in female rats.

Our objective was to evaluate the changes in melatonin synthesis during the peripubertal period in the female rat and to determine the effects of ovarian steroid hormones on melatonin synthesis. Pineal levels of tryptophan, 5-hydroxytryptamine (5-HT), melatonin and norepinephrine were determined in female Sprague Dawley rats (between 2 and 12 weeks of age) in the mid-dark during the daily light/dark cycle. Melatonin levels increased with age, parallel to pineal growth, until 6 weeks of age, when the vaginal opening was found in 66.7% of rats, and significantly decreased until 8 weeks of age, when the vaginal opening was found in all rats. Norepinephrine began to increase earlier and reached a mature level at 4 weeks of age. Treatments with bilateral ovariectomy at 4, 6, and 8 weeks of age resulted in significant increases in melatonin and 5-HT levels, and significant decrease in tryptophan level at 2 weeks after ovariectomy. Treatments with ovariectomy at 6 weeks of age produced a consistent increase in 5-HT level and a consistent decrease in tryptophan level until 6 weeks after ovariectomy. However, melatonin levels increased until 2 weeks after ovariectomy, then decreased and reached a control level at 6 weeks after ovariectomy. Subcutaneous implantation of estradiol-17 beta capsule and daily subcutaneous injection of estradiol benzoate (E2B) (1.0 microgram, 20 micrograms) for two weeks in the rats ovariectomized at 4, 6, and 8 weeks of age resulted in significant decreases in melatonin and 5-HT levels and a significant increase in tryptophan level at 2 weeks after ovariectomy. A smaller dose of E2B (0.1 microgram) produced the same effects in the rats ovariectomized at 4, but not at 6 and 8 weeks of age. Administration of progesterone (200 micrograms/day) for 2 weeks did not produce any significant changes in melatonin, 5-HT, and tryptophan levels. Norepinephrine levels were not changed by any of the above treatments. These results suggest that estrogen, but not progesterone, can modulate nocturnal pineal melatonin synthesis in peripubertal female rats, and that the decline in the melatonin synthetic activity during the pubertal period might be related to the increasing levels of endogenous estrogen, which is secreted from the maturing ovary. The sites of action of the inhibitory effect of estrogen on the pineal melatonin synthesis may be multiple.

Age Factors↗

PubMed1997

Melatonin inhibits vasospastic action of hydrogen peroxide in human umbilical artery.

We evaluated the antioxidant property of melatonin as it relates to the vasospastic effect of hydrogen peroxide (H2O2) on the human umbilical artery. Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between weeks 37 and 39 of gestation. Changes in maximal potassium chloride (KCl)-induced tension were measured in arterial segments with intact endothelium. Segments were treated with H2O2 alone, or were pretreated either with an H2O2 scavenger (catalase, 2000 i.u.), a hydroxyl radical scavenger (mannitol, 10(-2) M), a nitric oxide-synthesis inhibitor (L-NG-monomethyl arginine, LNMA, 2 x 10(-4) M), or melatonin (10(-6) M to 10(-4) M). The effect of H2O2 (10(-4) M) on the relaxation induced by the calcium ionophore A23187 was also determined in arterial segments, with or without pretreatment with melatonin (10(-6) M, 10(-4) M). H2O2 (10(-6) M to 10(-4) M) potentiated vascular tension in a concentration-dependent manner (P < 0.0001). Pretreatment with LNMA significantly suppressed the vasospastic effect of H2O2 (P < 0.0001). Pretreatment with either catalase or mannitol significantly reduced the vasospastic effect of H2O2 (P < 0.005, P < 0.002, respectively). Melatonin also significantly reduced the vasospastic effect of H2O2 in a concentration-dependent manner (H2O2 10(-6) M, P < 0.0001 : H2O2 10(-5) M, P < 0.0001 : H2O2 10(-4) M, P < 0.00001). Pretreatment with H2O2 significantly inhibited the relaxation induced by the calcium ionophore A23187 (P < 0.005). Treatment with melatonin prior to exposure to H2O2 significantly restored the relaxation induced by A23187 (P < 0.005). Results suggest that H2O2 potentiates vascular tension in the human umbilical artery, perhaps by suppressing the endothelial synthesis of nitric oxide. Melatonin significantly suppressed the vasospastic effect of H2O2, possibly due to its ability to scavenge the hydroxyl radical.

Antioxidants↗

PubMed1997

Melatonin suppresses vasospastic effect of hydrogen peroxide in human umbilical artery: relation to calcium influx.

We evaluated the hydroxyl radical scavenging effect of melatonin on the vasospastic action induced by hydrogen peroxide in human umbilical artery. Helical sections were made of umbilical arteries obtained from healthy pregnant women who were delivered between 37 and 39 weeks of gestation. Changes in maximal potassium chloride (KCl, 10[-2] M)-induced tension were measured in umbilical artery segments with intact endothelium. Segments were treated with H(2)O(2) (10[-9] M to 10[-7] M) only, or were pretreated with an H(2)O(2) scavenger (catalase, 2,000 IU), a hydroxyl radical scavenger (mannitol, 10[-2] M), or melatonin (10[-8] M to 10[-6] M). The effect of H(2)O(2) on the response of the segments of umbilical artery to external calcium was determined. Changes in KCl-induced contraction were also determined in segments pretreated with an inhibition of intracellular calcium release (ryanodine, 10[-4] M) prior to exposure to H(2)O(2). Pretreating the segments of umbilical arteries with H(2)O(2) (10[-8] M, 10[-7] M) significantly potentiated the maximal contraction induced by KCl (P < 0.0001, P < 0.03, respectively). Pretreatment with either catalase or mannitol significantly reduced the vasospastic effect of H(2)O(2) (10[-8] M) (P < 0.0001, P < 0.0001, respectively). Melatonin also significantly reduced the vasospastic effect of H(2)O(2) (10[-8] M), in a concentration-dependent manner (P < 0.0001). H(2)O(2) (10[-8] M) significantly increased the contractile response to external calcium. Melatonin pretreatment significantly suppressed the contractile response to external calcium. Treatment with ryanodine prior to exposure to H(2)O(2) did not affect KCl-induced contraction. Results suggest that H(2)O(2) potentiates the KCl-induced maximal contraction of the human umbilical artery, perhaps by increasing calcium influx via activation of the voltage-dependent calcium channel. Melatonin significantly suppresses the vasospastic effect of H(2)O(2), probably due to its scavenging of the hydroxyl radical.

Adult↗

PubMed1997

Effect of nitric oxide, prostacyclin, and thromboxane on the vasospastic action of hydrogen peroxide on human umbilical artery.

BACKGROUND: The effect of hydrogen peroxide (H2O2) on vascular tone in the human umbilical artery was investigated to determine the mechanism of vasospasm in preeclampsia. METHODS: Helical sections of the umbilical artery were obtained from healthy pregnant women who delivered between the 37th and 39th week of gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (PG F2 alpha) were measured (isometric mechanical activity). Segments were treated with H2O2 alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals (mannitol), an inhibitor of thromboxane synthesis (sodium ozagrel), and an inhibitor of nitric oxide synthesis (L-NG-monomethyl arginine, LNMA), or an inhibitor of prostacyclin synthesis (tranylcypromine, TCP). RESULTS: Vascular tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H2O2. Removal of the endothelium decreased the vascular tension induced by H2O2. Treatment with TCP and LNMA potentiated the vascular tension. Pretreatment with TCP and LNMA reduced the vasospastic action of H2O2, whereas pretreatment with sodium ozagrel did not. CONCLUSION: Vascular tension in human umbilical arteries was potentiated by H2O2, and may be mediated by a suppression of the activity of nitric oxide or of prostacyclin. A direct action of H2O2 on vascular smooth muscle may also be involved.

Epoprostenol↗

PubMed1997

Vasospastic action of hydrogen peroxide in human umbilical artery: relation to protein kinase C and calcium influx.

BACKGROUND: We have demonstrated that hydrogen peroxide (H2O2) potentiated vascular tension in human umbilical artery, perhaps by suppressing the synthesis of nitric oxide and prostacyclin. This study was conducted to evaluate whether the activation of protein kinase C (PKC) or voltage-dependent calcium channel mediated the vasospastic effect of H2O2. METHODS: Helical sections of the umbilical artery were obtained from healthy pregnant women who delivered between 37th and 39th week of gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (9 x 10(-7) M) were measured (isometric mechanical activity). Segments were treated with H2O2 (10(-6)-10(-4) M) alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals (mannitol, 10(-2) M), an inhibitor of PKC (H-7, 6 x 10(-7) M). Effect of an activator of PKC (12-tetradecanoyl phorbol-13 acetate, TPA, 10(-6) M) on PG F2 alpha-induced tension was determined. Effects of H2O2 (10(-5) M) on the response of umbilical artery segments to an external calcium (10(-6)-10(-3) M) were determined. RESULTS: Vascular tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H2O2. Pretreatment with H-7 did not alter the response to H2O2. TPA did not produce a significant change in PG F2 alpha-induced tension. Pretreatment with H2O2 (10(-5) M) did not alter the contractile response to external calcium. CONCLUSION: H2O2 potentiated vascular tension in human umbilical arteries, a process that is independent of PKC and the voltage-dependent calcium channel. The vasospastic effect of H2O2 may be mediated by a suppression of the activity of nitric oxide and prostacyclin.

Analysis of Variance↗

PubMed1996

Relaxant effect of nitric oxide and prostacyclin on serotonin-induced vasocontraction of human umbilical artery.

BACKGROUND: We investigated the effect of nitric oxide and prostacyclin, which are endothelium-derived vasodilators, on serotonin (5-HT)-induced vasocontraction, and 5-HT1-serotoninergic receptor mediated relaxation in the human umbilical artery. METHODS: Serotonin-stimulated vasocontraction was measured in umbilical artery segments treated with and without 1) L-arginine (10(-4) M approximately 10(-2) M), a precursor of nitric oxide synthesis; 2) methylene blue (10(-5) M) and L-NG-monomethyl arginine (LNMA, 2 X 1O(-4) M), which are specific inhibitors of nitric oxide action and nitric oxide synthesis, respectively; and 3) tranylcypromine (2 X 10(-6) M, 2 X 10(-5) M), an inhibitor of prostacyclin synthesis. 4) Vessels were pretreated with M1, an inhibitor of 5-HT2 serotoninergic receptors, and then prostaglandin F2 alpha (9.O X 1O(-7) M). Finally, we measured the 5-HT1, receptor-mediated relaxation induced by 5-HT. RESULTS: Treatment with L-arginine significantly inhibits 5-HT-induced contraction in a dose-dependent manner. Treatment with methylene blue and LNMA significantly potentiated 5-HT-induced contraction. Tranylcypromine caused no significant changes in 5-HT-induced vasocontraction. 5-HT1 serotoninetic receptor-mediated relaxation was found at higher concentrations of 5-HT (greater than 4.94 X 10(-5) M). CONCLUSIONS: Our results suggest that nitric oxide may exert a strong relaxant effect on 5-HT-induced vasocontraction compared with prostacyclin in human umbilical artery.

Arginine↗

PubMed1996

Potentiating effect of hydrogen peroxide on the serotonin-induced vasocontraction in human umbilical artery.

BACKGROUND: Our objective was to investigate the role of hydrogen peroxide in the vasocontraction induced in the human umbilical artery by serotonin. METHODS: Umbilical arteries collected from healthy women at term were cut helically and suspended in an organ bath to record isometric mechanical activity. In Study I, we measured the concentration-contraction response to serotonin with or without pretreatment with hydrogen peroxide (0.01-10 microM). In Study 2, vessels were pre-incubated with L-arginine (0.1-10mM), or with hydrogen peroxide (10 mM) and L-arginine (1 mM), then serotonin was added cumulatively. In Study 3, vessels were suspended in a calcium-free solution containing potassium chloride 20 mM, and a cumulative concentration-response curve to calcium chloride (10(-5)-10(-3) M) was constructed for vessels pretreated with hydrogen peroxide (10 microM). In Study 4, vessels were pre-treated with M1, an inhibitor of 5-HT2 serotoninergic receptors, and hydrogen peroxide (10 microM), and then prostaglandin F2 alpha (9.0 x 10(-7) M). Finally, we measured the 5-HT1 receptor-mediated relaxation induced by serotonin. RESULTS: Hydrogen peroxide (1 or 10 microM) significantly potentiated the contractile response to serotonin (p < 0.04, p < 0.005). L-arginine (1 or 10 mM) significantly reduced the contractile response to serotonin (p < 0.02, p < 0.0002). Pretreatment with L-arginine significantly suppressed the potentiating effect of hydrogen peroxide on the serotonin-induced contraction. The sensitivity of the arteries to calcium chloride in the presence of hydrogen peroxide did not differ from that in the control group. Pretreatment with hydrogen peroxide significantly reduced the 5-HT1 serotoninergic receptor-mediated relaxation at higher concentrations of serotonin (1.23 x 10(-4) M, 2.47 x 10(-4) M, 2.47 x 10(-4) M). CONCLUSION: Hydrogen peroxide potentiated the umbilical artery contraction induced by serotonin. This action may be mediated by suppression of endogenous nitric oxide activity.

Arginine↗

PubMed1995

Amplifying effect of endothelin-1 on serotonin-induced vasoconstriction of human umbilical artery.

OBJECTIVE: The purpose of this study was to evaluate the role of endothelin-1 in serotonin-induced vasoconstriction in human umbilical artery. STUDY DESIGN: Umbilical arteries collected from 41 normal subjects at term were cut helically and suspended in an organ bath for recording isometric mechanical activity. In study 1 we measured the concentration-contraction response to serotonin or endothelin-1 according to a cumulative concentration schedule. In study 2 vessels were preincubated with a subthreshold concentration of endothelin-1 (100, 250, or 500 pg/ml), and then serotonin was added cumulatively. In study 3 vessels were preincubated with H-7 (3 x 10(-6) mol/L), an inhibitor of protein kinase C, or with 12-tetradecanoylphorbol-13 acetate (10(-9) to 10(-7) mol/L), an activator of protein kinase C; then serotonin was added cumulatively. In study 4 vessels were suspended in a calcium-free solution containing 2 mmol/L ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid and 60 mmol/L potassium chloride, and then a cumulative concentration-response curve to calcium chloride (10(-7) to 10(-3) mol/L) was constructed for vessels pretreated with endothelin-1, 500 pg/ml or 5 ng/ml. RESULTS: The threshold concentrations of serotonin and endothelin-1 were 5 and 1 ng/ml, respectively. A subthreshold concentration of endothelin-1 (250 or 500 pg/ml) potentiated significantly the concentration response to serotonin (p < 0.084, p < 0.009, by analysis of variance). Pretreatment with H-7 significantly suppressed the amplifying effect of endothelin-1 on serotonin-induced contraction. Treatment with 12-tetradecanoylphorbol-13 acetate (10(-7) or 10(-8) mol/L) significantly potentiated the contractile response to serotonin (p < 0.0003, p < 0.015). The sensitivity of the arterial segments to calcium chloride in the presence of a subthreshold concentration of endothelin-1 did not differ from that in the control group. CONCLUSION: Endothelin-1 at a subthreshold concentration amplified the smooth muscle contraction induced by serotonin. The mechanism of action may be mediated by activation of intracellular protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1995

Enhanced nocturnal melatonin secretion in women with functional secondary amenorrhea: relationship to opioid system and endogenous estrogen levels.

The purpose of this study was to evaluate the role of the opioid system and the estrogen environment in the nocturnal secretion of melatonin in women with secondary amenorrhea (SA). Nocturnal melatonin concentrations in patients with SA were significantly higher than in normal women (p < 0.01 vs. women with normal menstrual cycles). There were significant negative correlations between cumulative melatonin levels (between 8 p.m. and 8 a.m.) and serum estradiol-17 beta (r = -0.561, p < 0.01) and between peak serum melatonin values and serum estradiol-17 beta concentrations (r = -0.608, p < 0.01) in SA. Intravenous administration of a conjugated estrogen (Premarin 20 mg) significantly suppressed nocturnal melatonin secretion (p < 0.05), but a continuous intravenous infusion of naloxone (1.6 mg/h from 8 p.m. to 6 a.m.), an opiate antagonist, did not affect nocturnal melatonin secretion in SA. Our findings suggest that elevated nocturnal melatonin secretion may be related to low estrogen levels, but that it is not mediated by the opioid system.

Adolescent↗

PubMed1995