Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 235 records · Page 13Linked to original sources

PubMed1998

Power Doppler sonography for hepatocellular carcinoma: factors affecting the power Doppler signals of the tumors.

AIMS/BACKGROUND: A recent advancement in Doppler ultrasonography (US) is power Doppler for detecting low-velocity blood flow at the microvascular level with angle independence. The present study was performed to characterize the factors contributing to the power Doppler signals of hepatocellular carcinoma (HCC). METHOD: Correlation of Doppler signals of HCC in 114 patients with 178 HCC nodules was analyzed in relation to the findings of CT and angiography, tumor characteristics (size, echo pattern, and histological differentiation of tumor), viral markers and severity of liver disease. RESULTS: The sensitivity of power Doppler US was superior to that of CT and angiography (each p<0.05; McNemar's test). The detection rate of power Doppler signal was significantly higher in tumors with diameter > or =2 cm (vs <2 cm in diameter), and with low/mixed echo pattern (vs high echo appearance), and with moderately/poorly differentiated HCC (vs well-differentiated HCC). Univariate analysis revealed that echo pattern, tumor size and histological differentiation of HCC in addition to CT and angiographic findings were significant. Multivariate analysis showed that tumor size and differentiation were significant. CONCLUSION: These results indicate that tumor characteristics play an important role in power Doppler signals and that these could be assessed by the presence or absence of power Doppler signals.

Angiography↗

PubMed1998

Use of a gastric juice-based PCR assay to detect Helicobacter pylori infection in culture-negative patients.

A gastric juice-based PCR assay was compared with culture, microscopy, and a rapid urease test with specimens from 114 subjects. The PCR and conventional tests were positive for 76 and 62% of the subjects, respectively. The prevalence of gastroduodenal disease and seropositivity for anti-Helicobacter pylori immunoglobulin G were similarly high among conventional-test-positive and PCR-only-positive subjects compared to all-negative ones. The PCR assay is recommended to confirm the H. pylori status of culture-negative peptic-ulcer patients.

Adult↗

PubMed1998

Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan.

BACKGROUND: VacA and CagA proteins have been reported to be major virulence factors of Helicobacter pylori. However, antibodies against these proteins are frequently found in the sera of Japanese patients regardless of their gastroduodenal status. AIM: To evaluate the expression of VacA and CagA proteins by H pylori strains isolated in Japan. METHODS: By using specific antibodies raised against recombinant VacA and CagA proteins, the expression of VacA and CagA was evaluated in 68 H pylori strains isolated from Japanese patients; a vacuolating assay and genotyping of the vacA gene were also used in the evaluation. The results in analysed in relation to the gastroduodenal diseases of the hosts. RESULTS: VacA and CagA proteins were expressed in 59/68 (87%) and in 61/68 (90%) isolates respectively. The vacuolating assay was positive in 57/68 (84%) isolates, indicating that most immunologically VacA positive strains produced active cytotoxin. The prevalence of infection with strains expressing CagA and positive for vacuolating activity (Type I) was very high, 54/68 (79%), irrespective of the gastroduodenal status of the host. CONCLUSION: Most H pylori isolates in Japan are positive for vacuolating cytotoxin and CagA, and thus these virulence factors cannot be used as markers to discern the risk of developing serious gastroduodenal pathologies in the hosts. However, the high prevalence of infection with strains positive for vacuolating cytotoxin and CagA may contribute to the characteristics of H pylori infection in Japan.

Adult↗

PubMed1998

Helicobacter pylori specific nested PCR assay for the detection of 23S rRNA mutation associated with clarithromycin resistance.

BACKGROUND: Clarithromycin is one of the most important antibiotics for Helicobacter pylori eradication. However, 5-10% of strains are reported to be resistant. It has been shown that one point mutation in the 23S rRNA gene is associated with resistance to clarithromycin. AIMS: To establish a polymerase chain reaction (PCR) system which amplifies a segment of the 23S rRNA gene containing the mutation points with primers specific for H pylori, so that H pylori infection and the mutation associated with clarithromycin resistance can be examined simultaneously. METHODS: To detect H pylori infection and the mutation simultaneously, primers specific for the H pylori 23S rRNA gene were designed based on sequence conservation among H pylori strains and sequence specificity as compared with other bacteria. DNA from 57 cultured strains and from 39 gastric juice samples was amplified in the seminested 23S rRNA PCR. Clinical applicability was evaluated in 85 patients. RESULTS: DNA samples from 57 cultured strains were all amplified. The novel assay and the urease A PCR agreed in 37/39 gastric juice samples with no false positives. The assay did not amplify the DNA of bacteria other than H pylori. Eight of 85 samples had the mutation before treatment. In clarithromycin based treatment, eradication was achieved in 2/5 (40%) with the mutation and 29/34 (85%) without the mutation. CONCLUSION: The assay using gastric juice is quick (within 12 hours) and non-invasive (endoscopy not required), enabling rapid initiation of appropriate antibiotic treatment.

Anti-Bacterial Agents↗

PubMed1998

Mesangial expression of a nonmuscle myosin heavy chain, SMemb, is associated with glomerular sclerosis and renal prognosis in IgA nephropathy.

To characterize the phenotypic alteration in mesangial cells in human glomerulonephritis, we investigated the expression of nonmuscle-type myosin heavy chain, SMemb, and alpha-smooth muscle actin (alpha-SM actin) in IgA nephropathy. The expression of SMemb and alpha-SM actin was examined by immunohistochemistry in biopsy specimens from 45 patients with IgA nephropathy. We examined a total of 489 glomeruli representing all patients enrolled, and found that mesangial expression of SMemb and alpha-SM actin was associated with mesangial proliferation. Only mesangial expression of SMemb showed a significant relationship with mesangial matrix accumulation. Semiquantitative evaluation using composite expression scores showed that the expression of SMemb was elevated in the patients with poor renal prognosis. The expression of alpha-SM actin showed no significant relationship with renal prognosis. These results suggest that mesangial expression of SMemb is an important factor in the progression of IgA nephropathy, and that SMemb and alpha-SM actin are associated with the activation of mesangial cells by different mechanisms.

Adolescent↗

PubMed1998

Altered myocardial vasodilatation in patients with hypertriglyceridemia in anatomically normal coronary arteries.

Reduced myocardial vasodilatation (MVD) in hypercholesterolemics without overt coronary stenosis has been reported. However, the status of MVD in hypertriglyceridemics has not yet been clarified. The aim of this study was to investigate whether MVD is impaired in patients with hypertriglyceridemia without overt coronary stenosis. Twenty-three hypertriglyceridemics (10 normocholesterolemic hypertriglyceridemics [HTGs] and 13 mixed combined hyperlipidemics [MCHLs]) and 13 age-matched controls were studied. All patients were proven to have more than one normal coronary artery, as diagnosed by coronary angiography, and those segments that were perfused by anatomically normal coronary arteries were used in the study. Myocardial blood flow (MBF) during dipyridamole (DP) loading and baseline MBF were measured by using positron emission tomography and [13N]ammonia, after which MVD was calculated. Baseline MBF (mL.min(-1).100 g(-1)) was comparable among HTG (76.0+/-26.1), MCHL (77.0+/-26.1), and controls (80.3+/-38.5). However, MBF during DP loading was significantly lower in MCHL (159+/-52.5) than in control subjects (292+/-166, P<.01), while it was comparable in HTG (202+/-104) and controls. MVD was significantly reduced in both HTG (2.70+/-1.09, P<.05) and MCHL (2.07+/-.70, P<.01) compared with controls (3.73+/-1.14). MVD in MCHLs tended to be reduced compared with that in HTGs, but the difference was statistically insignificant (P=.08). There was a significant relationship between MVD and both plasma triglycerides (r=-.47, P<.01) and plasma total cholesterol (r=-.55, P<.01). When controls and HTGs were combined, the relationship between MVD and plasma total triglycerides became more prominent (r=-.55, P<.05), and the significant relationship between cholesterol level and MVD disappeared. Multivariate regression analysis has revealed that the triglyceride level (F=5.2, P<.05) was independently related to MVD (r=.69, P<.01). In conclusion, MVD was reduced in hypertriglyceridemics in anatomically normal coronary arteries. Hypertriglyceridemia is an independent factor for this abnormality.

Aged↗

PubMed1998

Angiotensin-Converting Enzyme Inhibition Delays Onset of Glucosuria With Regression of Renal Injuries in Genetic Rat Model of Non-Insulin-Dependent Diabetes Mellitus.

BACKGROUND: The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non-insulin-dependent diabetes mellitus (NIDDM). We investigated whether angiotensin inhibition influences the onset of NIDDM and brings about a regression of renal injury in diabetes mellitus. METHODS AND RESULTS: Six-week-old OLETF rats were treated with the angiotensin-converting enzyme (ACE) inhibitors imidapril or enalapril for 16 weeks. Systolic blood pressure is increased in an age-dependent manner in OLETF rats. In this study, the elevation in systolic blood pressure was dose-dependently reduced by ACE inhibitor treatment. In OLETF rats, plasma concentrations of insulin and glucose increased and the glucosuria occurred at the age of 22 weeks. Simultaneously, OLETF rats exhibited proteinuria and nodular lesions in glomeruli. The ACE inhibitor treatment almost completely reduced glucosuria, and also decreased plasma concentrations of insulin and glucose in OLETF rats. ACE inhibitor treatment lessened the proteinuria and attenuated morphologically the severity of nodular lesions in OLETF rats. Moreover, increases in plasminogen activator inhibitor 1 (PAI-1) in OLETF rats were reduced by the ACE inhibitor treatment, and the improvement of glomerular lesions was related to decreases of PAI-1 and angiotensin II levels in plasma but not to improvement of glucose metabolism. CONCLUSIONS: ACE inhibitors delay onset of NIDDM with attenuation of kidney injury. The regression of kidney lesions is probably due to angiotensin reductions but not to glucose metabolism per se. ACE inhibitor drug therapy may be useful in preventing NIDDM and the subsequent renal injury in patients with NIDDM.

Journal Article↗

PubMed1998

Uniqueness of pilsicainide in class Ic antiarrhythmics.

Pilsicainide, a class Ic agent, is known to be an effective drug particularly for treating atrial tachyarrhythmias. However, its electrophysiological effects on the atrium have not been well studied. To characterize the electrophysiologic effects of pilsicainide on atrial myocytes in class Ic drugs, we examined the effects of this drug on membrane currents in single rabbit atrial myocytes using the tight-seal whole cell voltage-clamp technique. Under the current-clamp condition, pilsicainide did not affect the action potential duration at therapeutic ranges (< or = 3 microM) and slightly shortened it at higher concentrations (> or = 10 microM). These observations were quite different from those with other class Ic agents including flecainide and propafenone which prolong the atrial action potential duration. The drug did not affect the resting membrane potential. Under the voltage-clamp condition, pilsicainide inhibited the transient outward current (Ito) that is more prominent in the atrium than in the ventricle in a concentration-dependent manner. However, in contrast to other class Ic agents, the inhibition to Ito by pilsicainide was observed only at much higher concentrations (IC50-300 microM) and did not affect the inactivation time-course of Ito. Moreover, the drug (10 microM) did not significantly affect the Ca2+, delayed rectifier K+, inward rectifying K+, acetylcholine-induced K+ or ATP-sensitive K+ currents. From these results pilsicainide could be differentiated as a pure Na+ channel blocker from other class Ic agents with diverse effects on membrane currents and should be recognized accordingly in clinical situations.

Action Potentials↗

PubMed1998

Percutaneous hepatic infarction therapy for hepatocellular carcinoma.

OBJECTIVE: We percutaneously injected ethanol into small vessels afferent to tumor nodules to induce hepatic infarction in areas of tumor caused by hepatocellular carcinoma. CONCLUSION: Percutaneous hepatic infarction therapy holds promise as a new method of treating large hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMed1998

Hyperglycemia rather than insulin resistance is related to reduced coronary flow reserve in NIDDM.

To clarify if coronary flow reserve (CFR) is related to insulin resistance or hyperglycemia in normotensive NIDDM, myocardial blood flow (MBF) at baseline and during dipyridamole loading were measured with 13N-ammonia positron-emission tomography. CFR was significantly reduced in NIDDM patients compared with age-matched control subjects. CFR in patients with well-controlled NIDDM was significantly higher than in those with poorly controlled NIDDM, whereas insulin resistance was comparable between the two groups. CFR in NIDDM patients was not related to the degree of insulin resistance. CFR correlated significantly with average fasting glucose concentration and average HbA1c, but not with insulin resistance, age, lipid parameters, or blood pressure. In conclusion, control of blood glucose concentration rather than insulin resistance is most likely related to the reduced CFR in NIDDM.

Adult↗

PubMed1998

Organ-specific insulin resistance in patients with noninsulin-dependent diabetes mellitus and hypertension.

UNLABELLED: Abnormal heart and skeletal muscle glucose metabolism in diabetes or essential hypertension has been demonstrated. However, the role of hypertension in heart and skeletal muscle glucose utilization in diabetes has not been clarified yet. METHODS: We compared heart and skeletal muscle glucose utilization using PET and the whole-body glucose disposal rate (GDR) during insulin clamping in 9 patients with noninsulin-dependent diabetes mellitus (NIDDM) and essential hypertension and 11 patients with NIDDM without hypertension to examine the effect of hypertension on heart and skeletal muscle glucose utilization. Results also were compared with those for 8 asymptomatic healthy control participants. RESULTS: Skeletal muscle glucose utilization rate was comparable between hypertensive NIDDM patients (61.2 +/- 55.5 micromol x min(-1) x kg(-1)) and normotensive NIDDM patients (50.9 +/- 25.2 micromol x min(-1) x kg(-1)) but was significantly reduced in both groups compared with control subjects (94.2 +/- 57.3 micromol x min(-1) x kg(-1)), as was the GDR (25.2 +/- 11.3 and 24.0 +/- 7.5 micromol x min(-1) x kg(-1)), respectively, for patients compared with 38.5 +/- 11.5 micromol x min(-1) x kg(-1) for control participants). However, the myocardial glucose utilization (MGU) rate was significantly reduced in NIDDM patients without hypertension (389 +/- 185 micromol x min(-1) x kg(-1)) than in those with hypertension (616 +/- 86.4 micromol x min(-1) x kg(-1), p < 0.01). Multivariate stepwise regression analysis has shown that MGU was significantly correlated with systolic blood pressure and plasma free fatty acid concentration. CONCLUSION: Whole-body insulin resistance was observed in NIDDM patients independent of hypertension. The MGU rate may have different properties to oppose insulin resistance than glucose utilization of skeletal muscle in hypertensive patients with NIDDM.

Case-Control Studies↗

PubMed1997

Does dual infection by hepatitis B and C viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan?

BACKGROUND: There are contradictory data concerning the synergistic effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the progression from chronic hepatitis to hepatocellular carcinoma (HCC). METHODS: To clarify the role of coinfection with HBV and HCV in the progression and pathogenesis of HCC, viral and clinicopathologic features were studied in 368 consecutive HCC patients at the University of Tokyo from 1991-1995. RESULTS: Approximately 83% of patients (305 patients) were seropositive for the HCV antibody ("C-viral") and approximately 10% (37 patients) were positive for the hepatitis B surface antigen ("B-viral"). Positivity for both (dual infection) was found in only 2% of patients, and negativity for both in 5%. The incidence of dual infection in HCC patients was Similar to that in 549 patients with chronic hepatitis (1%) and 119 patients with cirrhosis (1%). Of the six HCC patients with dual infection, five patients were positive for the HBV early antigen and HBV DNA was less than measurable, whereas HCV RNA was detected and ranged from 10(3)-10(6) copies/50 microL of serum by competitive reverse transcriptase-polymerase chain reaction, and the clinical features resembled those of "C-viral" HCC. The remaining patient was early antigen positive and had HBV DNA by slot blot analysis, but the serum HCV RNA level was less than measurable. These data indicate that mutually exclusive viral replication occurred in patients with persistent coinfection. To further clarify further the possible involvement of HBV infection in "C-viral" HCC, HBV core antibody (HBcAb) was tested in 192 patients and was found to be positive in 111 and negative in 81. The serum HCV RNA level and clinicopathologic features (such as age and the severity of liver disease) were similar among the "C-viral" HCC patients irrespective of the presence or absence of HBcAb. CONCLUSIONS: Based on these results, coinfection was found to be much less prevalent than generally is claimed, and even in a few HCC patients with the coinfection the mutually exclusive viral replication was noted, suggesting that coinfection plays little if any role in the development of HCC.

Adult↗

PubMed1997

Promoters of epithelialization induce expression of vascular endothelial growth factor in human gastric epithelial cells in primary culture.

Both epithelialization and angiogenesis are indispensable processes in gastric ulcer healing. Coordination between these processes has not been well studied. In the present study, we have established a new primary culture system of human gastric epithelial cells and investigated the effect of epithelialization stimulants on a specific angiogenic factor, vascular endothelial growth characterized as epithelial cells. Both epithelialization stimulants, hepatocyte growth factor (HGF) and epidermal growth factor (EGF), significantly stimulated vascular EGF expression in gastric epithelial cells. HGF and EGF receptors were expressed by the cells, suggesting that regulation may be mediated through specific receptors.

Adult↗

PubMed1997

Reduced myocardial flow reserve in non-insulin-dependent diabetes mellitus.

OBJECTIVES: We analyzed myocardial flow reserve (MFR) in patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM) without symptoms and signs of ischemia. BACKGROUND: Diminished MFR in diabetes has been suggested. However, it remains controversial whether MFR is related to glycemic control, mode of therapy or gender in NIDDM. METHODS: Myocardial blood flow (MBF) was measured at baseline and during dipyridamole loading in 25 asymptomatic, normotensive, normocholesterolemic patients with NIDDM and 12 age-matched control subjects by means of positron emission tomography and nitrogen-13 ammonia, after which MFR was calculated. RESULTS: Baseline MBF in patients with NIDDM ([mean +/- SD] 74.0 +/- 24.0 ml/min per 100 g body weight) was comparable to that in control subjects (73.0 +/- 17.0 ml/min per 100 g). However, MBF during dipyridamole loading was significantly lower in patients with NIDDM (184 +/- 99.0 ml/min per 100 g, p < 0.01) than in control subjects (262 +/- 120 ml/min per 100 g), as was MFR (NIDDM: 2.77 +/- 0.85; control subjects: 3.8 +/- 1.0, p < 0.01). A significantly decreased MFR was seen in men (2.35 +/- 0.84) compared with women with NIDDM (3.18 +/- 0.79, p < 0.05); however, no significant differences were found in terms of age, hemoglobin a1c and baseline MBF. MFR was comparable between the diet (2.78 +/- 0.80) and medication therapy groups (2.76 +/- 0.77) and was inversely correlated with average hemoglobin A1c for 5 years (r = -0.55, p < 0.01) and fasting plasma glucose concentration (r = -0.57, p < 0.01) but not age or lipid fractions. CONCLUSIONS: Glycemic control and gender, rather than mode of therapy, is related to MFR in NIDDM.

Blood Glucose↗

PubMed1997

In vivo selective gene expression and therapy mediated by adenoviral vectors for human carcinoembryonic antigen-producing gastric carcinoma.

Previously, we reported that adenoviral vectors carrying the carcinoembryonic antigen (CEA) promoter sequences to direct the Echerichia coli beta-galactosidase gene (AdCEA-lacZ) or cytosine deaminase (CD) gene (AdCEA-CD) confer selective gene expression on a CEA-positive gastric cancer cell line (MKN45) in vitro. Here, adenovirus-mediated tumor-specific gene therapy for CEA-positive gastric carcinoma in vivo was investigated. Using an animal model with i.p. disseminated MKN45 tumors, adenovirus-mediated tumor-specific transgene expression and therapeutic efficacy were analyzed. After an i.p. injection of AdCEA-lacZ, beta-galactosidase activity was confined to tumor xenografts. Moreover, CD mRNA was expressed exclusively in MKN45 tumor xenografts after infection with AdCEA-CD, despite the fact that an adenovirus-mediated transfer of CD DNA was detected in all tissues tested. In contrast, CD mRNA was detected not only in tumor xenografts but also in other organs of mice infected with AdCA-CD, in which CD gene expression is governed by an ubiquitous promoter. Suppression of tumor growth and prolongation of survival were noted in tumor-bearing mice treated with AdCEA-CD and 5-fluorocytosine (5FC) without observable adverse effects. In contrast, significant hepatic toxicity was noted in animals treated with AdCA-CD. These results reveal that the CEA promoter restricts CD gene expression to CEA-positive tumor cells in the adenoviral context in vivo, along with the beneficial therapeutic effects of 5FC treatment, suggesting the i.p. AdCEA-CD/5FC system may provide a novel approach to treatment of i.p. disseminated gastric cancer.

Animals↗

PubMed1997

Characterization of a specific region in the hepatitis B virus enhancer I for the efficient expression of X gene in the hepatic cell.

Hepatitis B virus (HBV) enhancer I has been shown to consist of several cis-acting sequences for the HBV gene expression efficiently in certain types of cells. Transcriptional regulation of HBV X gene mediated by enhancer I might be one of the mechanisms by which HBV obtains hepatotropism. By mutagenesis analysis of enhancer I function in the enhancer I/X gene promoter complex, we characterized a specific transcriptional regulatory region (designated as a LSR element, nt 989-1030) of enhancer I for the X gene promoter by means of the transient transfection technique using hepatic and nonhepatic cells. Based on the analysis of protein factors interacting with the LSR element, liver-enriched transcriptional factors, HNF3 and HNF4 or retinoid X receptor alpha (RXR alpha), are probably implicated in the activity of enhancer I for the efficient expression of X gene through their interaction with the LSR element in the hepatic cell. Furthermore, the isolated LSR element was demonstrated to function alone as a specific cis-acting element and to be able to activate transcription from the X gene promoter efficiently in the hepatic cell in an orientation-independent manner.

Base Sequence↗

PubMed1997

Circadian variation of paroxysmal atrial fibrillation.

BACKGROUND: Circadian variation in the incidence of acute cardiovascular events is well known but has not been extensively investigated in paroxysmal atrial fibrillation, although the significance of this arrhythmia is growing in our society with the increasing number of aged people. METHODS AND RESULTS: We detected 150 patients with paroxysmal atrial fibrillation in a drug-free state from among 25,500 consecutive Holter recordings. To determine whether the onset, maintenance, and termination of paroxysmal atrial fibrillation were random events, we analyzed the total recorded duration of arrhythmia and the incidence of and number of patients with the onset, maintenance, and termination of this arrhythmia as hourly data and as hourly probabilities. A prominent circadian rhythm of the total duration of atrial fibrillation, approximately 90% of which was well explained by a single cosinusoidal function, was detected with a nadir around 11 AM. Because the onset of the arrhythmia had little or no circadian rhythm, this finding was due to a diurnal pattern of maintenance and termination, both of which were well expressed by a double-harmonic density function. Maintenance showed a trough at 11 AM, and termination showed a peak at the same time, leading to the nonuniform duration of single episodes of atrial fibrillation throughout the 24-hour day. CONCLUSIONS: Paroxysmal atrial fibrillation showed a unique circadian variation that differed from the well-known pattern for acute cardiovascular events, a point that should be kept in mind when antiarrhythmic therapy is evaluated. Identification of factors that regulate the circadian pattern of the maintenance and termination of paroxysmal atrial fibrillation may lead to better chronotherapy for preventing perpetuation of this arrhythmia.

Aged↗

PubMed1997

Effects of extracellular pH on receptor-mediated Ca2+ influx in A7r5 rat smooth muscle cells: involvement of two different types of channel.

1. The effects of extracellular pH (pHo) on receptor (vasopressin or endothelin-1)-mediated Ca2- entry and Ca(2+)-permeable channels were investigated in aortic smooth muscle cells (A7r5) from rat embryonic thoracic aorta. Intracellular Ca2+ ([Ca2+]i) was measured using fura-2 AM and whole-cell voltage clamp techniques were employed. 2. Vasopressin and endothelin-1 (100 nM) in the presence of nicardipine (10 microM) evoked a sustained rise in [Ca2+]i due to calcium entry. Extracellular acidosis decreased receptor (vasopressin or endothelin-1)-mediated Ca2+ entry, while extracellular alkalosis potentiated it. 3. Depletion of intracellular Ca2+ stores with thapsigargin (1 microM) also evoked Ca2+ entry activated by emptying of intracellular Ca2+ stores (capacitative Ca2+ entry). Extracellular acidosis decreased this capacitative Ca2+ entry, while extracellular alkalosis potentiated it. 4. Under voltage-clamp conditions with Ca+ internal solution, vasopressin and endothelin-1 activated non-selective cation currents (ICAT). Ba2+ or Ca2+ were also charge carriers of ICAT. Reducing the pHo inhibited ICAT, while increasing pHo potentiated it in a reversible manner. 5. Intracellular pH (pHi) changes did not cause the same marked effects as pHo changes, and a high concentration of Hepes (50 mM) in the patch pipette did not inhibit the effects of pHo on ICAT. 6. Similar results were obtained when ICAT was activated by GTP gamma S (1 mM) applied through the patch pipette, even in the absence of agonists, probably because of direct activation of GTP-binding proteins coupled to the receptors. 7. In cells treated with thapsigargin, addition of Ca2+ to the bath solution induced Ca(2+)-dependent K+ currents activated by capacitative Ca2+ entry. However, no measurable ionic currents activated by capacitative Ca2+ entry (ICRAC) were observed under conditions with Cs+ internal solution and EGTA (5 mM), although vasopressin still activated ICAT. 8. These results suggest that the contractile agonists vasopressin and endothelin-1 evoked Ca2+ entry through two different types of Ca(2+)-permeable channel (ICAT and ICRAC) and pHo affects these channels, which may modulate receptor-mediated Ca2+ influx in A7r5 cells. Thus, pH-induced changes of these channels may play a pathophysiological role in the control of receptor-mediated contractions.

Animals↗