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Biomedical subjects

M Shichiri

Publications and source records attributed to M Shichiri.

At least 199 records · Page 11Linked to original sources
PubMed1989

Vasoconstrictor-induced heterologous down-regulation of vascular atrial natriuretic peptide receptor.

Long-term (24 h) pretreatment of cultured rat vascular smooth muscle cells with 100 nM angiotensin and 1 microM vasopressin induced a marked reduction of the maximal binding capacity of atrial natriuretic peptide (ANP) receptors in a fashion similar to that induced by phorbol ester. The down-regulation of the receptors induced by vasoconstrictors and phorbol ester was concomitantly associated with an attenuation of ANP-stimulated cGMP accumulation. These data suggest that vasoconstrictor-induced activation of protein kinase C is involved in the mechanism of heterologous down-regulation of vascular ANP receptors.

Angiotensin II↗
PubMed1989

Specific receptor for endothelin in cultured rat cardiocytes.

Specific binding sites for the endothelium-derived vasoconstrictor endothelin (ET) and its effect on cytosolic free Ca2+ concentrations [( Ca2+]i) were studied in a primary culture of cardiocytes from neonatal rats. Binding studies using 125I-labeled-porcine ET as a radioligand revealed the presence of a single class of high-affinity binding sites for ET in cardiocytes with an apparent Kd of 6-9 x 10(-10) M and a Bmax of 50,000-80,000 sites/cell. Neither various vasoconstrictors nor Ca2+-channel blockers affected the binding. Pretreatment with ET substantially reduced the total number of ET receptors without changing their affinity. ET dose-dependently increased [Ca2+]i in fura-2-loaded cardiocytes. These data indicate that cardiocytes have specific ET receptors that are controlled by a down-regulation mechanism, and that ET induces a receptor-mediated increase in [Ca2+]i in cardiocytes.

Animals↗
PubMed1989

Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells.

To elucidate the cellular mechanism by which endothelin (ET) is secreted, we have studied the effects of a variety of vasoactive agents on the secretion of immunoreactive (IR)-ET from cultured bovine endothelial cells (EC). Confluent bovine EC cultured in serum-free medium secreted IR-ET as a function of time. Not only thrombin, but also vasoconstrictive hormones, such as arginine-vasopressin (AVP) and angiotensin (ANG) II, dose-dependently stimulated IR-ET secretion, and these effects were completely abolished by V1-receptor antagonist and [Sar1,Ala8]-ANG II, respectively. Protein kinase C (PKC)-activating phorbol ester and Ca2+ ionophore ionomycin had stimulatory effects on IR-ET secretion, and the combination of both compounds had a synergistic effect. These data suggest that AVP and ANG II, like thrombin, stimulate ET secretion from EC by a mechanism possibly involving receptor-mediated mobilization of intracellular Ca2+ and activation of PKC.

Angiotensin II↗
PubMed1989

Receptor binding activity and cytosolic free calcium response by synthetic endothelin analogs in cultured rat vascular smooth muscle cells.

Using a variety of synthetic analogs of porcine endothelin (pET), we have studied the effects of these analogs on receptor binding activity and cytosolic free Ca2+ concentrations ([Ca2+]i) in cultured rat vascular smooth muscle cells (VSMC). Removal of C-terminal Trp21 residue, truncated derivatives pET(1-15) and (16-21), substitution of disulfide bond, Cys(3-11) or Cys(1-15), by Cys (Acm), all resulted in a complete loss of receptor binding activity and [Ca2+]i response, while N-terminal elongation of Lys-Arg residues, but not oxidation of Met7 residue, decreased receptor binding activity and [Ca2+]i response. [Cys1-15,Cys3-11]pET was far more potent than [Cys1-11,Cys3-15]pET in receptor binding and [Ca2+]i response. These data indicate that the C-terminal Trp21 as well as the proper double cyclic structure formed by the intramolecular disulfide bonds of the pET molecule are essential for receptor binding and subsequent [Ca2+]i increase in rat VSMC.

Animals↗
PubMed1989

Presence of immunoreactive endothelin in human plasma.

A highly specific and sensitive radioimmunoassay has been established for measurement of human endothelin (hET) in human plasma. After extraction of plasma with an octyl-silica column, this assay allowed for detection of immunoreactive (IR) hET as low as 0.2 fmol/ml. In 16 healthy subjects, the mean concentration of plasma IR-hET was 0.6 fmol/ml. Reverse-phase HPLC coupled with radioimmunoassay revealed two major IR-hET components, one corresponding to authentic hET(1-21) and another with more hydrophilicity than hET(1-21). These data indicate that ET is a circulating vasoconstrictor hormone in man.

Adult↗
PubMed1989

Simultaneous evaluation of insulin secretion and action using a model.

For the simultaneous evaluation of insulin secretion and insulin sensitivity, a glucose regulation model has been developed. In order to estimate the parameters of the model, an intravenous glucose infusion test (GIT, 100 mg/kg.min x 2 min and 10 mg/kg.min x 118 min) was carried out on 15 healthy subjects (N), 12 subjects with impaired glucose tolerance (IGT), 20 non-insulin-dependent diabetics (NIDDM) and 13 patients with chronic pancreatitis (CP). The coefficient (microU/mg) for insulin secretion depending on blood glucose concentration in IGT, NIDDM and CP were lower (35.9 +/- 2.7, 24.5 +/- 3.3, 43.1 +/- 3.1) than in N (77.5 +/- 7.9). The coefficients (microU.min/mg) for insulin secretion depending on rate of change in blood glucose concentration in IGT and NIDDM were significantly lower (6.5 +/- 2.1, 3.8 +/- 1.2) than in N (52.8 +/- 8.8). The insulin sensitivity index (ISI; 10(-2) mg/(microU/ml).kg.min) in NIDDM was lower (4.98 +/- 0.75) than in N (11.37 +/- 1.08). Administration of exogenous insulin did not significantly affect the value of ISI in N and NIDDM. ISI showed a tendency to increase (15.09 +/- 1.92) in CP. It was demonstrated that the proposed model which estimates both insulin secretory ability and insulin sensitivity simultaneously is quite useful for analyzing the mechanism of impaired glucose tolerance.

Adult↗
PubMed1989

Effectiveness of insulin suppositories in diabetic patients.

Experimental insulin suppositories regulated postprandial hyperglycaemia in diabetic patients. The insulin suppositories seemed also to avoid hyperinsulinaemia. The formulation with more rapid dissolution of insulin, which contained a solid dispersed form of insulin, effectively reduced the insulin dose required.

Adult↗
PubMed1989

Degradation of atrial natriuretic peptide in dogs.

To clarify the degradation of atrial natriuretic peptide (ANP) in dogs, plasma ANP concentrations in blood samples drawn from the coronary sinus, and in simultaneously collected blood samples of the arteries and veins of the lung, liver, kidney, spleen and cervix, and of the supramesenteric artery and the portal vein, were measured, both when infused with exogenous ANP (280 ng.kg-1.min-1, N = 7) and when not infused (N = 6). Venous ANP concentrations in most organs showed lower values than arterial levels by 11.6 to 33.6%, suggesting degradation during circulation. Exogenous ANP infusion resulted in a 26.0 to 41.9% arterio-venous decrease in ANP levels. These findings suggest that each organ contributes to ANP degradation, and that no specific organ plays a key role. The plasma ANP concentration was not reduced when blood samples were incubated for 60 min at 37 degrees C. The plasma from the coronary sinus and forearm vein contained essentially identical ANP molecular forms, as shown by gel permeation chromatography. Thus, the blood circulation through various organs does not cause high molecular weight ANP to be changed to other forms.

Animals↗
PubMed1988

Brain natriuretic peptide interacts with atrial natriuretic peptide receptor in cultured rat vascular smooth muscle cells.

The effect of synthetic porcine brain natriuretic peptide (pBNP), a novel brain peptide with sequence homology to alpha-human atrial natriuretic peptide (hANP), on receptor binding and cGMP generation, was studied in cultured rat vascular smooth muscle cells (VSMC) and compared with that of alpha-hANP. 125I-pBNP bound to the cells in a time-dependent manner similar to that of 125I-alpha-hANP. Scatchard analysis indicated a single class of binding sites for pBNP with affinity and capacity identical to those of alpha-hANP. pBNP and alpha-hANP were almost equipotent in inhibiting the binding of either radioligand and stimulating intracellular cGMP generation. These data indicate that BNP and ANP interact with the same receptor sites to activate guanylate cyclase in rat VSMC.

Animals↗
PubMed1988

Red-cell-volume distribution curves in diagnosis of glomerular and non-glomerular haematuria.

The distribution curves of urinary red-blood-cell (RBC) size were obtained from automated blood-cell analysis in 146 patients with definite causes of haematuria. In 65 of 67 patients (97%) with haematuria and glomerulonephritis demonstrated by renal biopsy, urinary RBC had an irregular and asymmetrical distribution with RBC size showing a much smaller volume than that of venous RBC. This "glomerular" distribution contrasted with the "non-glomerular" normal distribution when the peak for RBC was at a larger volume than that for peripheral RBC. In 46 of 47 patients with haematuria who had lower urinary tract lesions other than infection, a non-glomerular distribution was obtained; 30 of these cases also showed glomerular distribution, and were classified as "mixed". All 32 patients with urinary tract infection had either a glomerular or mixed distribution, suggesting that they excreted distorted and dysmorphic urinary RBC. After excluding infections, this simple, rapid, reproducible, and non-invasive technique provides reliable information in distinguishing glomerular bleeding from other causes of haematuria.

Diagnosis, Differential↗
PubMed1988

Effect of alpha 2-adrenoceptor antagonist on platelet activation during insulin-induced hypoglycaemia in type 2 (non-insulin-dependent) diabetes mellitus.

The role of epinephrine in platelet activation and the effect of an alpha 2-adrenoceptor antagonist, midaglizole, during insulin-induced hypoglycaemia in Type 2 (non-insulin-dependent) diabetes mellitus were examined. The action of midaglizole as a platelet alpha 2-antagonist was confirmed by in vitro studies using platelet-rich plasma and washed platelet suspension. Hypoglycaemia was induced by a bolus injection of short-acting insulin in 24 diabetic patients. They were divided into two groups, a control group (n = 12) and an alpha 2-group (n = 12), and midaglizole was administered orally 60 min before insulin injection in the latter. Blood glucose and plasma C-peptide levels were significantly decreased (p less than 0.005) by insulin injection in both groups. Counter-regulatory hormones, including epinephrine, and arginine vasopressin were similarly increased at the hypoglycaemic nadir compared with the levels at 0 min in both groups. Plasma beta-thromboglobulin was increased at the hypoglycaemic nadir (165.5 +/- 12.6 ng/ml) compared with the level at 0 min (121.0 +/- 11.5, p less than 0.005) in the control group, whereas no significant increase was demonstrated in the alpha 2-group. These results suggest that plasma epinephrine plays an important role in platelet activation during hypoglycaemia in Type 2 diabetes mellitus, and that the platelet activation is prevented by alpha 2-adrenoceptor antagonist.

Arginine Vasopressin↗
PubMed1988

Influence of apolipoprotein E polymorphism on plasma lipid and apolipoprotein levels, and clinical characteristics of type III hyperlipoproteinemia due to apolipoprotein E phenotype E2/2 in Japan.

Apolipoprotein (apo) E phenotype was examined in 188 healthy subjects and in 447 patients seen between 1984 and 1986. The frequency of the apo E2, 3, and 4 genes in the clinically healthy subjects was 0.035 +/- 0.0288, 0.872 +/- 0.0310, and 0.093 +/- 0.0152, respectively. The frequency of the apo E3 gene was higher and that of the apo E genes 2 and 4 lower than that reported in western countries. Clinical features and apo E phenotype are presented from the 5 patients with type III hyperlipoproteinemia (HLP) due to apo E phenotype E2/2 (E2-III); all patients in E2-III were post-menopausal women. In contrast to the clinical characteristics so far reported, no notable findings of atherosclerosis, such as coronary angiographic findings or xanthoma, were evident in any of these 5 patients. Glucose intolerance was seen in 4 of them. Four patients were normolipidemic with apo E phenotype E2/2 (E2-N). In addition, plasma lipid and apolipoprotein concentrations were determined in patients with different apo E phenotypes. Plasma total cholesterol (TC) and apo B levels were elevated in the order of E2-N, E2/3, E2/4, E3/3, E3/4 and E4/4 except for E2-III. The plasma apo E level was highest in E2-III but was not significantly different from other phenotypes. The apo B/apo E and apo C-III/apo E ratios were significantly lower in E2/2 than in other phenotypes. The TC/apo B ratio was significantly higher in E2/2 than in other phenotypes.

Adult↗