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Biomedical subjects

I Kusumi

Publications and source records attributed to I Kusumi.

36 records · Page 2Linked to original sources
PubMed1994

Serotonin-induced platelet intracellular calcium mobilization in depressed patients.

Serotonin(5-HT)-stimulated intracellular calcium(Ca) mobilization was measured in the platelets of depressed patients to assess 5-HT2 receptor function. The 5-HT-induced Ca response was significantly higher in unmedicated patients with bipolar depression and melancholic major depression than in those with non-melancholic major depression and normal controls. The enhanced Ca response to 5-HT failed to correlate with severity of depressive symptoms. In patients with bipolar disorder and melancholic major depression, there was no significant difference in 5-HT-stimulated Ca response between the unmedicated group and those in remission. These results suggest that 5-HT2 receptor function is increased in some types of depression, and raise the possibility that the enhanced Ca response to 5-HT may be trait dependent rather than state dependent.

Adult↗
PubMed1994

Effect of mood stabilizing agents on agonist-induced calcium mobilization in human platelets.

The effect of mood stabilizing agents such as lithium, carbamazepine, valproic acid and clonazepam on serotonin(5-HT)- or thrombin-induced intracellular calcium (Ca) mobilization was studied in the platelets of healthy subjects using the fluorescent Ca indicator fura-2. After incubating platelet-rich plasma with these drugs for one or four hours, there was no significant difference in either basal Ca2+ concentration or 5-HT-stimulated Ca response between each agent treatment and control. 5-HT- or thrombin-induced Ca mobilization was not altered by four weeks of lithium carbonate administration in healthy volunteers. These results indicate that these mood stabilizers fail to affect the agonist-stimulated intracellular Ca mobilizing pathway either in vitro or ex vivo in the platelets of healthy subjects.

Adult↗
PubMed1993

Dopamine D1, D2 and serotonin2 receptor occupation by typical and atypical antipsychotic drugs in vivo.

In vivo occupation of dopamine D1 and D2 and serotonin (5-HT)2 receptors by typical and atypical antipsychotic drugs (APD) was examined using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, which nonselectively and irreversibly inactivates these receptor sites. APD were classified as typical or atypical based on their capacity to induce extrapyramidal side effect in humans and/or catalepsy in laboratory rodents. Pretreatment of rats with typical APD (haloperidol, 0.25-3 mg/kg; chlorpromazine, 5-10 mg/kg; cis-flupenthixol, 1 mg/kg; zotepine, 5 mg/kg; nemonapride, 0.5-2 mg/kg) potently reversed the N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline-induced D2 receptor inactivation in rat striatum. In contrast, some atypical APD or its candidates (clozapine, 5-30 mg/kg; fluperlapine, 10 mg/kg; risperidone, 0.25-3 mg/kg; setoperone, 0.025-0.25 mg/kg; ORG 5222, 0.25 mg/kg) showed considerable occupation of 5-HT2 receptors in cerebral cortex with smaller or negligible occupation of D2 and D1 receptors. Pretreatment with the other atypical APD (sulpiride, 30 mg/kg; amperozide, 1 mg/kg) had no effect on these three receptors, although at higher doses, sulpiride (60 mg/kg) and amperozide (5 mg/kg) slightly but significantly reversed D2 and 5-HT2 receptor inactivation, respectively. It was concluded that a certain group of atypical APD is characterized by high occupancy of 5-HT2 receptor with lower or minimal occupancy of D2 and D1 receptors in vivo. The relevance of these characteristics of atypical APD was discussed in relation to extrapyramidal side effects and the therapeutic effects on schizophrenia.

Animals↗
PubMed1993

[Serotonin-2 receptor-mediated intraplatelet calcium mobilization in affective disorders: relevance to the pathophysiology of depression].

Abnormal serotonin-2(5-HT2) receptor function in the central nervous system has been suggested to play a role in the pathogenesis of affective disorders. The presence of 5-HT2 receptors on human platelet similar to those in brain may permit direct study of 5-HT2 receptor function in living persons. 5-HT-stimulated intracellular calcium (Ca) concentration change was studied in the platelets of healthy subjects, using fluorescent Ca indicator fura-2. 5-HT increased the Ca response in a concentration-dependent manner. The maximal response was obtained at 10 microM of 5-HT and its EC50 value was 0.4 microM. This response was potently inhibited by selective 5-HT2 receptor antagonists, suggesting that the 5-HT-induced Ca mobilization is mediated by 5-HT2 receptors. This 5-HT-stimulated Ca response was not significantly affected by the time of blood sampling, gender, age, meal or exercise. Therefore, it may be concluded that the 5-HT-induced Ca response in human platelets is a stable parameter and that it is suitable for assessing 5-HT2 receptor function in depressed patients. Thus, the 5-HT-induced Ca mobilization was measured in the platelets of depressed patients. The response was significantly higher in unmedicated patients with bipolar depression and melancholic major depression than in those with non-melancholic major depression and normal controls. The enhanced Ca response to 5-HT failed to correlate with severity of depressive symptoms. In patients with bipolar depression and melancholic major depression, there was no significant difference in 5-HT-stimulated Ca response between unmediated group and euthymic-treated group. These results suggest that 5-HT2 receptor function is increased in some type of affective disorders and that the enhanced Ca response to 5-HT may be trait dependent rather than state dependent.

Adult↗
PubMed1991

Effect of various factors on serotonin-induced Ca2+ response in human platelets.

Serotonin (5-HT)-stimulated intracellular Ca2+ concentration change was studied in the platelets of healthy subjects, using fluorescent Ca indicator fura-2. 5-HT increased the Ca2+ response in a concentration-dependent manner. 10 microM of 5-HT induced the maximal response and its EC50 value was 0.4 microM. This response was potently inhibited by selective 5-HT2 antagonists, suggesting that 5-HT-induced Ca2+ mobilization in human platelets is mediated by 5-HT2 receptors. This 5-HT2-mediated Ca2+ response was not significantly affected by the time of blood sampling, gender, meal or exercise. However, this response declined with time after blood drawing, suggesting that it must be measured as soon as possible after sampling. These results indicate that 5-HT-stimulated Ca2+ response in human platelets is a stable parameter and that it will be suitable for assessing 5-HT2 receptor function in depressed patients.

Adolescent↗
PubMed1991

Increased 5-HT-2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients.

1. The present study was undertaken to examine whether or not 5-HT-induced inositol monophosphate (IP-1) accumulation in human platelets is mediated by 5-HT-2 receptors and to assess 5-HT-2 receptor function as measured by 5-HT-stimulated IP-1 accumulation in platelets from normal controls and depressed patients before drug treatment. 2. In platelets prelabeled with 3H-myo-inositol, in Ca ion free HEPES buffer containing 10 mM LiCl, 5-HT caused a dose-dependent accumulation of IP-1 during 15 min incubation. A maximal increase in IP-1 formation was observed at 30 microM of 5-HT and its EC50 value was 4 microM. 3. Ketanserin, a selective 5-HT-2 antagonist, was a potent inhibitor of 5-HT-stimulated IP-1 accumulation with a Ki value of 12 nM, but (-)propranolol (10 microM), a 5-HT-1 antagonist, failed to block the 5-HT response. 4. The potencies of various compounds tested to inhibit 5-HT-stimulated IP-1 accumulation in human platelets correlated positively with the affinities to 5-HT-2 receptor as defined by radioligand binding in rat cerebral cortex. 5. In a group of unmedicated patients with major depressive disorder matched for age with normal control group, we found a significant increase in 5-HT (100 microM)-induced accumulation of IP-1 (150 +/- 7% of basal for depressed patients, 132 +/- 3% for controls).

Adult↗
PubMed1991

Effect of subchronic antidepressants administration on serotonin-stimulated phosphoinositide hydrolysis in para-chlorophenylalanine-treated rat hippocampal slices.

1. This study examines the effect of subchronic parachlorophenylalanine (PCPA) treatment upon serotonin (5-HT)-stimulated inositol monophosphate (IP-1) accumulation in rat hippocampal slices and also the effect of antidepressants upon this 5-HT response in the hippocampus from rats treated with or without concurrent administration of PCPA. 2. For high dose PCPA treatment, animals were injected intraperitoneally with 300 mg/kg daily for the first 5 days and then 100 mg/kg for 5 days, while for low dose PCPA treatment animals were injected for 10 days at a dose of 100 mg/kg. Imipramine or iprindole (15 mg/kg i.p.) was given once daily for 10 consecutive days. 3. 10-Day treatment with high dose of PCPA resulted in a significant increase in 5-HT-stimulated IP-1 accumulation, whereas low dose of PCPA had no significant effect upon the 5-HT response as compared to vehicle. 5-HT-stimulated IP-1 accumulation in rat hippocampus was not affected by subchronic treatment with imipramine or iprindole. The enhancement of the 5-HT response induced by high dose of PCPA was not attenuated by repeated antidepressants treatment.

Animals↗
PubMed1990

Subchronic administration of para-chlorophenylalanine enhances serotonin-stimulated phosphoinositide hydrolysis in rat hippocampal slices.

Serotonin (5-HT) caused a dose-dependent accumulation of inositol monophosphate (IP-1) in rat hippocampal slices (maximal effect + 172%, EC50 = 630 nM) in the presence of LiCl. The 5-HT response was blocked potently by a non-selective 5-HT receptor antagonist metergoline and a 5-HT1C/5-HT2 receptor antagonist ritanserin. The 5-HT2 receptor antagonist ketanserin and spiperone were, however, less potent at inhibiting the 5-HT response. m-Chlorophenylpiperazine (mCPP), a 5-HT1C receptor agonist but a 5-HT2 antagonist stimulated directly PI turnover, yet mCPP inhibited 5-HT-stimulated PI response. These findings indicate that both 5-HT1C and 5-HT2 receptors are involved with a complicated interaction of each receptor in 5-HT-stimulated PI hydrolysis in rat hippocampus. 10-Day treatment with para-chlorophenyl-alanine (PCPA), a 5-HT synthesis inhibitor, resulted in a significant increase (maximal effect + 225%, EC50 = 580 nM) in 5-HT-stimulated IP-1 accumulation with no substantial change in EC50 value, which suggest that subchronic treatment with PCPA enhances the 5-HT-mediated PI hydrolysis in rat hippocampus.

Animals↗
PubMed1990

Serotonin-induced acute desensitization of serotonin2 receptors in human platelets via a mechanism involving protein kinase C.

Serotonin (5-HT)-induced changes in the levels of intracellular Ca++ were analyzed in human platelets, using the Ca+(+)-sensitive dye 1-(2-(5'-carboxyoxazol-2'-yl)-6-aminobenzofuran-5-oxy)-2-(2' -amino-5'- methylphenox)-ethane-N,N,N',N'-tetraacetic acid, pentaacetoxymethyl ester, to investigate the regulation of 5-HT2 receptor function. Serotonin mobilized intracellular Ca++ in a dose-dependent fashion from basal level of 98 +/- 2.7 and up to 211 +/- 5.8 nM with an EC50 value for 5-HT of 0.2 microM. Ketanserin, a 5-HT2 antagonist, reversed the 5-HT (10 microM)-induced Ca++ increase in a dose-dependent manner with an IC50 value of 2 nM. An initial treatment with 10 microM 5-HT abolished the response to a second treatment with 100 microM 5-HT, suggesting that 5-HT evoked an acute desensitization of 5-HT2 receptors in human platelets. Mezerein and phorbol 12-myristate 13-acetate, activators of protein kinase C, inhibited 5-HT-stimulated inositol monophosphate accumulation with IC50 values of 3 and 10 nM, respectively. Furthermore, a protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride prevented the protein kinase C activator-induced inhibition against 5-HT-mediated inositol monophosphate accumulation. Mezerein also inhibited 5-HT (10 microM)-mediated Ca++ release with an IC50 value of 3 nM. 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride prevented the inhibition by mezerein of the 5-HT-stimulated Ca++ increase. Moreover, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride by itself enhanced the Ca++ spike induced by 100 microM 5-HT, the plateau phase induced by 10 microM 5-HT and the second response to 5-HT. These findings suggest that 5-HT2 receptor activation mobilizes intracellular Ca++ in human platelets and that this receptor may be desensitized acutely by a protein kinase C mediated feedback system.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1978

Successive spontaneous abortions including one with whole-arm translocation between chromosomes 2.

A family with five induced and seven spontaneous abortions and no live births is described. Four of the seven spontaneous abortuses were available for cytogenetic examination and three were successfully karyotyped. Their karyotypes were 46,XX; 46,XX/46,XX,t(2;2)(2p2p;2q2q); and 46,XY. The karyotypes of the parents were normal. The origin of the 2p/2p and 2q/2q translocation in one of the abortuses was assigned to an interhomologous whole-arm translocation in an early mitotic division in a conceptus with a 46,XX karyotype.

Abortion, Habitual↗
PubMedDate not supplied

Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum.

Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum were studied. Repeated administration of citalopram increased the amount of dopamine D2 receptors, the level of dopamine D2 receptor mRNA, and the transcription rate of the dopamine D2 receptor gene. Single administration of citalopram also increased the level of dopamine D2 receptor mRNA with a maximum effect in 2-4 h after the treatment, and the transcription rate of the dopamine D2 receptor gene. The administration of 5-hydroxytryptophan (5-HTP) also increased the level of dopamine D2 receptor mRNA. These results suggest that the increase in the dopamine D2 receptor expression induced by citalopram may be owing, at least partially, to the stimulation of the dopamine D2 receptor gene transcription, and that serotonin (5-HT) may mediate the effects of citalopram in the induction of dopamine D2 receptor expression.

5-Hydroxytryptophan↗
PubMedDate not supplied

Differential expression of matrix metalloprotease-7 in each component of uterine carcinosarcoma.

The aim of this study was to investigate the expression of matrix metalloprotease-7 (MMP-7) in each component of uterine carcinosarcoma. Surgical specimens of primary tumors of uterine carcinosarcomas were obtained from 13 patients. The carcinomatous component consisted of adenocarcinoma with or without squamous differentiation. The sarcomatous component consisted of spindle cell sarcoma, chondrosarcoma and rhabdomyosarcoma, either alone or in combination. The immunohistochemical expression of MMP-7 protein was examined using the avidin-biotin peroxidase complex technique employing the anti-MMP-7 monoclonal antibody. Expression of MMP-7 protein was detected in 9 (69.2%) of 13 adenocarcinoma components, while no staining was observed in any of the sarcomatous components examined. There was a statistically significant difference of the positive rate for MMP-7 between epithelial components and sarcomatous components of uterine carcinosarcoma (p<0.01). In some cases, MMP-7 was abundantly expressed at the invasive front of adenocarcinomas. It is concluded that MMP-7 protein is differentially expressed between the carcinomatous component and the sarcomatous component of uterine carcinosarcoma. Each component of carcinosarcoma may have its own potential for invasion and metastasis. MMP-7 may contribute to the invasive nature or growth capacity of the carcinomatous component of uterine carcinosarcoma, while it may not have a relation to that of the sarcomatous components.

Adenocarcinoma↗