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J Nishimura

Publications and source records attributed to J Nishimura.

At least 181 records · Page 10Linked to original sources
PubMed1994

Relationship between cytosolic calcium concentration and force in the papaverine-induced relaxation of medial strips of pig coronary artery.

1. The mechanisms of vasorelaxation induced by papaverine were investigated using front-surface fluorometry and fura-2-loaded medial strips of the pig coronary artery. 2. In the presence of extracellular Ca2+ (1.25 x 10(-3) M), histamine (10(-4) M) induced abrupt elevations of cytosolic calcium concentration, [Ca2+]i reaching a peak within 12 s (the first phase); after making a slight shoulder, [Ca2+]i declined gradually to reach sustained levels (the second phase). Force rapidly rose to reach maximum levels in 3 min, then gradually declined. Papaverine (10(-7)-10(-5) M) inhibited both the first and the second phases of [Ca2+]i elevation and the development of force induced by histamine, in a concentration-dependent manner. 3. In the absence of extracellular Ca2+, histamine (10(-4) M) induced a transient increase in [Ca2+]i and force, both of which were inhibited in a concentration-dependent manner by papaverine (10(-7)-10(-5) M). When papaverine was washed out, a second application of 10(-4) M histamine also induced transient increases in [Ca2+]i and force. The smaller the first response, the greater was the second response. The total amount of [Ca2+]i released from intracellular stores by the first and second application of histamine in the presence of papaverine was smaller than in its absence, thereby indicating a reduction of Ca2+ in the histamine-sensitive store. However, while papaverine (10(-5) M) did not affect the transient increase in [Ca2+]i induced by 2 x 10(-2) M caffeine, contractions were inhibited. 4. For a given level of [Ca2+]i, the force developed with the cumulative application of histamine(10-7 M-10-1 M) was greater than that observed with the cumulative application of extracellular Ca2+(0-7.5 x 10-3 M) during high K+ depolarization. Papaverine (10-7 M-10-5M) suppressed, in a concentration-dependent manner, the increase in [Ca2+]i and the force induced by cumulative applications of both histamine and extracellular Ca2+ during high K+ depolarization. The [Ca2+]i-force curve obtained by depolarization with K+, but not that obtained during histamine application, was shifted to the right by papaverine. Diltiazem, 10-7 M, a concentration causing a similar degree of relaxation to 10-5 M papaverine, did not shift the [Ca2+]i-force curve obtained with high K+. Nitroglycerin (10-6 M)and isoprenaline (10-6 M) shifted the [Ca2+]i-force curve to the right to a greater extent than did 10-5 M papaverine.5. These findings suggest that papaverine relaxes medial strips of the porcine coronary artery by two mechanisms. The first is mainly due to a decrease in [Ca2+]i, not only through inhibiting Ca2+ influx through either voltage-dependent or receptor-operated Ca2+ channels, but also by inhibiting agonist induced intracellular Ca2+ release. This occurs presumably by interference with the signal transduction pathway for histamine and by a depletion of Ca2+ in histamine-sensitive stores. Secondly, the [Ca2+]i-sensitivity of certain contractile mechanisms may be minimally decreased.

Animals↗
PubMed1994

Sensitivity of G-protein involved in endothelin-1-induced Ca2+ influx to pertussis toxin in porcine endothelial cells in situ.

1. We designed a new method to determine quantitatively the intracellular Ca2+ concentration ([Ca2+]i) in endothelial cells in situ, using front-surface fluorometry and fura-2-loaded porcine aortic valvular strips. Using this method, we investigated the characteristics of the G-protein involved in endothelin-1 (ET-1)-induced changes in [Ca2+]i of endothelial cells in situ. 2. Endothelial cells were identified by specific uptake of acetylated-low density lipoprotein labelled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL). Double staining with DiI-Ac-LDL and fura-2 showed that the valvular strip was covered with a monolayer of endothelial cells and that the cellular component which contributed to the fura-2 fluorescence, [Ca2+]i signal, was exclusively endothelial cells. 3. ET-1 (10(-7) M) induced an elevation of [Ca2+]i consisting of two components: the first was a rapid and transient elevation to reach a peak, followed by a second, sustained elevation (the second phase). The first phase was composed of extracellular Ca(2+)-independent and -dependent components, while the second phase was exclusively extracellular Ca(2+)-dependent. The extracellular Ca(2+)-independent component of the first phase was due to the release of Ca2+ from intracellular storage sites. The second phase and part of the first phase of [Ca2+]i elevation were attributed to the influx of extracellular Ca2+. The Ca2+ influx component was completely inhibited by 10(-3) M Ni2+ but was not affected by 10(-5) M diltiazem. 4. Pertussis toxin (IAP) markedly inhibited the extracellular Ca2+-dependent elevation of [Ca2+]j, but had no effect on the extracellular Ca2+-independent elevation of [Ca2+], caused by ET-1 (10-7M).5. Bradykinin (10-7 M) or ATP (10- 5M) elevated [Ca2+]i and these responses also consisted of extracellular Ca2+-independent and extracellular Ca2+-dependent components. IAP had no effect on either component of the [Ca2+]i elevation induced by bradykinin or ATP.6. From these findings we conclude that, in porcine endotheliel cells in situ, ET-1 elevates [Ca2+]i as are result of a Ca2+ influx component from the extracellular space and release of intracelluarly stored Ca2+ .The Ca2+ influx is regulated by an IAP-sensitive G-protein, while the release of Ca2+ from the intracellular store is not.

Animals↗
PubMed1994

Molecular basis of beta-thalassemia in Japan: heterogeneity and origins of mutations.

Characterization of beta-thalassemia mutations was attempted for 13 unrelated Japanese patients heterozygous for beta-thalassemia. We have systematically analyzed beta-thalassemia genes using polymerase-chain-reaction-related techniques; dot blot hybridization with oligonucleotide probes complementary to known mutations, restriction endonuclease assay and direct sequencing of amplified genomic DNA. Seven different mutations were detected. Six of them are an amber mutation in codon 90 (GAG to TAG), a four-base-pair deletion in codons 41 and 42 causing premature termination due to frameshift, a C-T substitution at position 654 of IVS-2, a G-A substitution at position 1 of IVS-2 and a C-G substitution at position 848 of IVS-2, leading to splicing defects, and an ocher mutation (GAA-TAA) in codon 121 causing a thalassemia intermedia phenotype with inclusion body formation in erythrocytes. A silent mutation (CTG-TTG) was also detected in codon 91 of the allele with the IVS-2 position 1 mutation. These mutations have been reported previously in the Japanese population. The other mutation is a novel one in the Japanese, an amber mutation (TGG-TAG) in codon 15, causing a beta zero-thalassemia phenotype by premature termination of the beta-globin chain synthesis. We analyzed haplotypes of chromosomes bearing each beta-thalassemia mutation. Origins and a spectrum of mutations in comparison with those detected in malaria-endemic regions are discussed.

Adolescent↗
PubMed1994

Analysis of mdr-1 gene expression in human leukemic cells by quantitative competitive PCR.

The ability to recognize the acquisition of multidrug resistance (MDR) in leukemia patients would improve our ability to predict the responsiveness of patients to chemotherapy. To quantitate the degree of MDR acquisition, we determined the amount of mdr-1 mRNA in leukemic cells from patients by competitive polymerase chain reaction (PCR) analysis. Twenty-one patients including 12 patients prior to treatment and nine relapsed patients with acute myelogenous or lymphoblastic leukemia were examined. The amount of mdr-1 gene expression in K562, K562/ADR500 cells and their mixtures showed a proportional correlation between the ratio of resistant to non-resistant cells and the amount of the mdr-1 gene. Mean mdr-1 gene expression in relapsed patients was greater than that in pretreatment patients. Patients refractory to chemotherapy (NR) showed higher levels of mdr-1 gene expression than the patients who achieved complete remission (CR). Because of the wide variations in values, no statistical differences were observed between pretreatment and relapsed patients, or CR and NR patients. These results suggest that the competitive PCR technique is a reliable method to quantitatively determine mdr-1 gene expression, but it may be difficult to predict responsiveness to chemotherapy by using this technique alone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Detection of bcr/abl mRNA in stained bone marrow smears.

We describe the polymerase chain reaction (PCR) method using stained bone marrow smears as sources of RNA. The amount of extractable RNA decreased during the process of making and staining bone marrow smears. The sensitivity of the reverse transcriptase-based polymerase chain reaction (RT-PCR) method for detecting target mRNA-positive cells in 5 x 10(5) suspended cells and stained bone marrow smears were 1:10(5) and 1:5000, when we used K562 cells. The bone marrow smears of 21 patients with chronic myelogenous leukemia (CML) were examined using this method. We extracted RNA from stained specimens stored at room temperature for 5-14 years. Twelve of 21 (57%) smears showed positive results for bcr/abl. The carrier RNA improved the recovery when added at the step of RNA extraction. These data indicate that mRNA is present in stained bone marrow smears for at least 14 years and that the sensitivity of RT-PCR is adequate for molecular analysis.

Base Sequence↗
PubMed1994

Effects of nicorandil on cytosolic calcium concentrations and on tension development in the rabbit femoral artery.

By using front-surface fluorometry and fura-2-loaded strips of the rabbit femoral artery, the effects of 2-nicotinamidoethyl nitrate (nicorandil) on cytosolic Ca++ concentration ([Ca++]i) and on tension development were measured simultaneously, and findings were compared with those of SG-209 (2-nicotinamidoethyl acetate), nitroglycerin and cromakalim. During contraction induced by 25 mM K(+)-depolarization or by 3 x 10(-7) M noradrenaline stimulation, application of nicorandil, nitroglycerin or cromakalim, decreased [Ca++]i and tension, in a concentration-dependent manner. With a given amount of reduction in [Ca++]i, the extent of relaxation was in the following order: nitroglycerin > nicorandil > cromakalim. The [Ca++]i-tension relations of the relaxations induced by nitroglycerin and cromakalim were shifted to the right and to the left from that observed with the nicorandil-induced relaxation, respectively. During the contraction induced both by 25 mM K(+)-depolarization and by 3 x 10(-7) M noradrenaline, glibenclamide almost fully antagonized cromakalim- and SG-209-induced relaxation, and partially antagonized the nicorandil-induced relaxation, but not the nitroglycerin-induced relaxation. In the absence of extracellular Ca++, the noradrenaline-induced contraction due to release of Ca++ from the intracellular store was inhibited by nicorandil and by nitroglycerin. Cromakalim and SG-209 had no such effects. Both nitroglycerin and nicorandil increased intracellular cyclic GMP content. We suggest that nicorandil relaxes the rabbit femoral artery both by directly reducing [Ca++]i and by directly controlling Ca++ sensitivity of the contractile apparatus, through second messengers. The reduction of [Ca++]i involves inhibition of the release of stored Ca++ and Ca++ influx, the latter due in part to opening of ATP-sensitive K+ channels.

Animals↗
PubMed1994

Detection of minimal residual disease in a patient with acute promyelocytic leukemia by RT-PCR: necessity of chemotherapy following ATRA therapy.

The PML/RAR alpha fusion gene resulting from the t (15;17) translocation is a specific marker for acute promyelocytic leukemia (APL). We examined bone marrow cells by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect residual PML/RAR alpha mRNA-containing cells following treatment with all-trans retinoic acid (ATRA) and cytotoxic chemotherapy in a patient with APL. This RT-PCR assay can detect one leukemic cell in 10(2) normal cells in vitro. We show that PML/RAR alpha mRNA was still detectable despite clinical remission following ATRA treatment, but undetectable following consolidation with chemotherapy. These data show that this technique is useful for the identification of minimal residual disease in patients with APL and that cytotoxic chemotherapy following ATRA therapy is required for the elimination of APL cells.

Base Sequence↗
PubMed1993

CD7+ stem cell leukemia/lymphoma. Features of a subgroup without circulating blast cells.

Recent advances in immunology have clarified the cellular origin of hematopoietic neoplasms. Blast cells with a CD7+ CD4- CD8- phenotype are demonstrated to originate from malignant pluripotent hematopoietic stem cells. In this article, the authors describe three rare cases, designated as a lymphoma type of CD7+ stem cell leukemia/lymphoma, with clinical features described below. All three patients were admitted with non-Hodgkin lymphoma with a 2-month to 4-month history of lymphadenopathy. Histologic examination of lymph nodes showed lymphoblastic lymphoma (LBL) in all patients. Bone marrow blast cells had an immunophenotype consistent with CD7+ CD4- CD8- acute leukemia, although abnormal cells were not observed in the peripheral blood during the course of the disease. One patient had a recurrence in the bone marrow, with myeloperoxidase-positive blast cells expressing myeloid differentiation antigens. Chromosomal analysis detected a common abnormal karyotype initially and at relapse. Furthermore, the same T-cell receptor gene rearrangement was found initially and at relapse, suggesting that these blast cells originated from the same pluripotent leukemic clone. Additional studies on more patients are required to determine the clinical significance of this group, including the difference from CD7+ stem cell leukemia/lymphoma with circulating blast cells (leukemic type) or LBL.

Acute Disease↗
PubMed1993

Median preoptic neurons projecting to the hypothalamic paraventricular nucleus are sensitive to blood pressure changes.

Twenty-one neurons in the median preoptic nucleus (MnPO) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) in male rats under urethane anesthesia. The activity of these identified neurons was tested for a response to activation of peripheral baroreceptors, achieved by rising arterial blood pressure with an intravenous administration of the alpha-agonist metaraminol. Of the neurons tested, 14 displayed a reduction and 2 exhibited an increase in neuronal excitability that accompanied a 30- to 50-mmHg elevation in mean arterial pressure, while 5 were unresponsive. The results show that efferent pathways from the MnPO to the PVN may receive neural inputs from the peripheral baroreceptors, suggesting the involvement of the pathways in the control of cardiovascular function.

Action Potentials↗
PubMed1993

Prognostic value of the number of metastatic lymph nodes in gastric cancer with radical surgery.

To evaluate the effectiveness of extended lymph node dissection in gastric cancer, the relationship between the number of lymph nodes with metastasis and the long-term outcome was studied retrospectively in 761 patients who underwent curative resection with extensive lymph node dissection. The cumulative 5-year survival rate was 85.8% in patients without lymph node metastasis, 60.2% in those with 1-4 lymph nodes, 35.6% with 5-10 nodes, and 12.3% with 11 or more nodes involved. Concerning N2 or N3 patients in whom metastatic lymph nodes would have remained without extensive dissection, the 5-year survival rate was 70.5% in those with 1-4 lymph nodes involved and 44.0% with 5 or more lymph nodes involved when no serosal invasion was observed. It was 38.5% with 1-4 lymph nodes and 5% with 5 or more lymph nodes involved when serosal invasion was observed. These results suggest that extensive lymph node dissection is effective in gastric cancer patients without serosal invasion and, when only a few lymph nodes are involved, also in those with serosal invasion. However, it is not considered to be effective in patients with serosal invasion and metastasis to many lymph nodes. Combination therapies are thought to be required in such patients.

Adult↗
PubMed1993

Double t(1;7)(p36;p11) in a megakaryocytic crisis of chronic myelogenous leukemia with variant t(5;9;22).

A 56-year-old man with chronic myelogenous leukemia (CML) who presented with a variant Ph chromosome, t(5;9;22)(q13;q34;q11), developed a unique additional chromosomal change of a double reciprocal t(1;7)(p36;p11) during the accelerated phase. A minor clone that had two copies of 1p+ and a copy of 7p- with a normal chromosome 7 was observed simultaneously. The patient underwent a megakaryocytic crisis. Surface marker of the blasts was positive for CD13, CD33, HLA-DR, CD41a, and CD42b, and negative for CD14 and lymphoid markers. Sequential chromosome analysis suggests that the double t(1;7) was caused by a multistep event consisting of duplication of both derivative chromosomes accompanied by loss of normal chromosomes 1 and 7. This may be the first report of a double reciprocal chromosomal translocation in a hematopoietic neoplasm.

Chromosome Banding↗
PubMed1993

Recurrent appearance of 14q+ chromosome associated with lymphoid crisis of Ph-positive chronic myelogenous leukemia.

The 14q+ chromosomal anomaly commonly found in cases of lymphoid neoplasm recurrently occurred during the lymphoid crisis of a patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). At presentation lymphoblasts, with pre-B phenotype increased, and both the Ph and 14q+ were found in the same metaphases. After treatment with vincristine and prednisolone, the patient entered into the chronic phase, and only a Ph was detected in 100% of the cells examined. The 14q+ reappeared at the recurrence of the lymphoid crisis, and then disappeared in the second chronic phase. The BCR/ABL mRNA, which is specific for CML, was detected in the blastic cells by a method using reverse transcriptase and polymerase chain reaction. The rearrangement of the immunoglobulin heavy chain gene (JH gene) was also detected in the blastic cells. These results suggest that the 14q+ was closely associated with the lymphoid crisis of the CML patient.

Chromosome Aberrations↗
PubMed1993

A study of the changes in the level of serum IgG4 antibody and soluble CD23 (s-CD23) in nasal allergy patients with immunotherapy.

Specific IgG4 antibodies were determined by enzyme-linked immunosorbent assay (ELISA), radio allergosorbent test (RAST), and s-CD23 in a total of 17 patients with nasal allergy who were given immunotherapy with house dust. The following results were obtained. 1) From the results between the serum antigen-specific IgG4 and the clinical effect of immunotherapy, there are many cases showing the elevation of antigen-specific IgG4 antibody titer. But in the elevated cases, there were only 7 cases showing good and excellent responses in a clinical effect of 41.1%. 2) IgG4 antibody was gradually elevated in many cases during immunotherapy, but in a few cases, abruptly increased after the maximum tolerated dose was established. 3) Regarding the outcome between IgG4 antibody and IgE antibody, cases of rising IgG4 and decreasing IgE occurred at a rate of 41%. 4) s-CD23 in sera gradually decreased in many cases during immunotherapy, but in a few cases, did not change.

Adolescent↗
PubMed1993

Effects of lidocaine on intracellular Ca2+ and tension in airway smooth muscle.

BACKGROUND: Many studies have demonstrated that lidocaine directly relaxes airway smooth muscle. The underlying mechanisms, especially in relation to Ca2+ mobilization, remain to be elucidated. METHODS: Using front-surface fluorometry and fura-2-loaded porcine tracheal smooth muscle strips, intracellular Ca2+ concentration ([Ca2+]i) and isometric tension were simultaneously measured. RESULTS: In cases of 40 mM K(+)-induced contraction and 1 microM acetylcholine (ACh)-induced contraction, the cumulative application of lidocaine (10(-6) approximately 3 x 10(-3) M) caused a concentration-dependent decrease in [Ca2+]i and tension, and almost complete relaxation. To examine the effect of lidocaine on Ca2+ sensitivity of the contractile apparatus, the [Ca2+]i-tension relationship was determined by changing the extracellular Ca2+ concentration during 40 mM K+ induced depolarization, with and without treatment with lidocaine. Although treatment with 1 mM lidocaine inhibited increases in both [Ca2+]i and tension induced by extracellular Ca2+, it had little effect on the [Ca2+]i-tension relationship. In the presence of 1 microM ACh, the [Ca2+]i-tension relationship shifted markedly to the left, thereby indicating an increase in Ca2+ sensitivity of the contractile apparatus; this shift was inhibited by 1 mM lidocaine. In the absence of extracellular Ca2+, 1 mM lidocaine inhibited the release of stored Ca2+ induced by 1 microM ACh, but not that by 20 mM caffeine. CONCLUSIONS: Lidocaine directly relaxes airway smooth muscle by decreasing [Ca2+]i. In addition, lidocaine inhibits the ACh-induced increase of Ca2+ sensitivity of the contractile apparatus, although it has little effect on Ca2+ sensitivity during high K+ depolarization. The decrease in [Ca2+]i is attributed to inhibition of the influx of extracellular Ca2+, as induced by high K+ depolarization and by ACh, and to the inhibition of the ACh-induced release of stored Ca2+.

Animals↗
PubMed1993

PML/RAR alpha fusion gene is expressed in both granuloid/macrophage and erythroid colonies in acute promyelocytic leukaemia.

Acute promyelocytic leukaemia (APL) associated with a t(15;17) translocation generates a PML/RAR alpha chimaeric gene which is transcribed as a fusion PML/RAR alpha mRNA. To clarify the pathophysiologic role of PML/RAR alpha in APL patients, we examined the expression of PML/RAR alpha in haemopoietic colonies in five patients with APL by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. By the two-step RT-PCR method, we demonstrated that PML/RAR alpha positive clones were present in progenitor cells including both CFU-GM and BFU-E in two cases. This result suggests that the translocation of PML/RAR alpha occurred in a pluripotent stem cell in some APL patients. In four patients we detected two amplified cDNA fragments of 780 and 640 bp which presumably arose by alternative splicing of the PML gene. Interestingly, of CFU-GM and BFU-E colonies examined in four patients, there were three different types of colonies: those expressing only the 780 bp fragment, those expressing only the 640 bp fragment, and those expressing both fragments. This suggests that alternative splicing was clonally determined in each colony. We describe a useful RT-PCR technique for the study of gene expression in a limited number of haemopoietic precursor cells.

Adult↗
PubMed1993

Clinicopathologic, enzyme and histochemical studies of centrocytic (mantle cell) lymphoma: comparison with other types of low-grade B cell lymphoma based on the updated Kiel classification.

Lymph nodes from 21 cases of malignant lymphoma of a centrocytic (mantle cell) type, (ML, cc (mc)) were examined. All the cases had monoclonal surface immunoglobulin (sig) M and/or D, but were negative for CD10 (CALLA), and CD11c (LeuM5). Lymphoma cells with CD25 (anti-Tac)+, CD5 (Leu1)+, and alkaline phosphatase (ALPase)- in eight cases showed bone marrow involvement (10-66% of the nucleated cells; mean 32 +/- 18%) but with no leukemic changes. These eight cases had a similar phenotype and were distributed by the lymphoma cells to the examined B-chronic lymphocytic leukemia. Seven cases showed an infiltration of CD25-, CD5+, and ALPase- lymphoma cells, in which only two cases showed focal bone marrow involvement. There was a close relationship between CD25 expression and bone marrow invasion by the lymphoma cells in ML, cc (mc). Three of the six CD25- and CD5- cases presented zonal proliferation of ALPase+ lymphoma cells with round nuclei and a high anti-proliferating cell nuclear antigen/cyclin (PCNA/c) rate in the mantle zone and paracortex, accompanied by a prominent interdigitating dendritic and histiocytic cell reaction. Examined CD25-, CD5- and ALPase+ lymphoma showed a neoplastic counterpart of so-called marginal zone lymphocytes, which was different from other cases of ML, cc (mc). Lymphoma cells in ML, cc (mc), except for those of the so-called marginal zone lymphoma, might be derived from slgM+, D+/-, CD25+/-, CD5+/-, ALPase-, CD10- and CD11c- lymphocytes present in the mantle zone and primary lymph follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of isoprenaline on cytosolic calcium concentrations and on tension in the porcine coronary artery.

1. Using front-surface fluorometry and fura-2-loaded medial strips of the porcine coronary artery, cytosolic Ca2+ concentration ([Ca2+]i) and tension development were simultaneously monitored in an attempt to determine the mechanisms of vasorelaxation induced by l-isoprenaline (Iso). 2. Iso actively decreased [Ca2+]i of the strips at rest, both in the presence and absence of extracellular Ca2+. 3. In the presence of extracellular Ca2+, depolarization with high-external K+ solution induced an elevation of [Ca2+]i and tension of the rapid increase and sustained, steady-state type; both levels depended on external K+ concentration. When Iso was applied at the time of steady state of high-K(+)-induced [Ca2+]i elevation, there was an initial transient reduction (the first component) followed by a subsequent sustained reduction (the second component) of [Ca2+]i. For a given [Ca2+]i level during high-K+ depolarization, the tension developed in the presence of Iso was smaller than that in its absence. Thus, the [Ca2+]i-tension relationship during the steady state of high-K(+)-induced contraction was shifted to the right by Iso. Pretreatment with ryanodine, a compound which depletes Ca2+ stored in the sarcoplasmic reticulum, abolished the first component, but not the second sustained decrease in [Ca2+]i by Iso. 4. In the presence of extracellular Ca2+ (1.25 mM), histamine (Hist) induced an abrupt (the first component) and then sustained (the second component) elevations of [Ca2+]i, while the tension rose rapidly to reach the peak, and then, gradually declined. The second, but not the first, component of [Ca2+]i elevation depended on extracellular Ca2+. Iso inhibited both the first and the second components of [Ca2+]i elevation and the contraction induced by Hist, in a concentration-dependent manner (IC50, 2 x 10(-8) M for the first component, and 5 x 10(-8) M for the second component). Cumulative application of Hist (10(-7)-10(-4) M) increased [Ca2+]i and tension with the [Ca2+]i-tension relationship shifting to the left from that observed with high K+. The [Ca2+]i-tension relationship during the Hist-induced contraction shifted to the right by Iso. In contractions induced by a higher concentration (> or = 6 x 10(-5) M) of Hist, despite the negligible decrease in [Ca2+]i, Iso could relax the muscle in a concentration-dependent manner. 5. In the absence of extracellular Ca2+, Hist induced transient elevations of [Ca2+]i and tension, possibly due to a release of Ca2+ from intracellular stores, and with similar time courses to those of the first component observed in the presence of extracellular Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗