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Biomedical subjects

Y Toya

Publications and source records attributed to Y Toya.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Molecular biology of alpha-adrenergic receptor and essential hypertension].

The primary physiological agents for adrenergic receptors are only two, epinephrine and norepinephrine, which have been used to differentiate alpha- and beta-adrenoceptors. The pharmacological properties can distinguish subtype alpha 1-, alpha 2-, beta 1- and beta 2-receptors. Recently additional subtypes have been characterized by radioligand binding techniques and molecular biological techniques. Molecular mechanisms of regulation as well as regulatory site of gene expression of alpha-adrenergic receptors has been extensively studied. In addition, the association analysis of alpha 2-adrenergic receptor gene RFLP in essential hypertension has been performed. Eventhough we could not find any association of an alpha 2 C10-Bsu36I RFLP with essential hypertension in Japan, the finding showed significant ethnic RFLP difference at the gene locus for alpha 2 C10. The association of alpha 2 adrenergic receptor RFLP with blood pressure has been also studied using F2 generations of SHR and WKY and Dahl salt sensitive rats and resistant rats. Further studies are now in progress to clarify the role of these alpha-adrenergic receptors in cardiovascular diseases.

Amino Acid Sequence↗
PubMed1992

Imaging of luciferase secretion from transformed Chinese hamster ovary cells.

The blue luminescence characteristic of the marine ostracod crustacean Vargula hilgendorfii is from a simple, but highly specific, enzyme-substrate reaction. Light is emitted by the oxidation of Vargula luciferin (substrate) by molecular oxygen, a reaction catalyzed by luciferase. Stable transformants of Chinese hamster ovary cells carrying the Vargula luciferase gene secreted luciferase from discrete sites on the cell surface, and this secretion could be monitored in real time by the bioluminescence produced by the secreted luciferase in the presence of Vargula luciferin by using an image-intensifying technique. Addition of anti-Vargula luciferase IgG to the luminescing cells almost completely extinguished the luminescence, confirming that Vargula luciferase caused the luminescence.

Animals↗
PubMed1992

Enhanced inhibitory effect of alpha 2-adrenoceptor stimulation on the formation of cAMP in glomeruli of spontaneously hypertensive rats.

Renal alpha 2-adrenoceptors are known to be increased in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). To investigate whether this difference affects the second messenger system, we examined the effect of alpha 2-adrenoceptor stimulation on the formation of cAMP in microdissected glomeruli and proximal convoluted tubules obtained from the kidneys of SHR and WKY. The formation of glomerular cAMP, which was stimulated by parathyroid hormone (PTH), was inhibited by alpha 2-adrenoceptor stimulation. In contrast, the inhibitory effect of alpha 2-adrenoceptor stimulation on PTH-induced cAMP formation in proximal convoluted tubules was not significantly different between SHR and WKY. These results confirm the inhibitory action of alpha 2-adrenoceptors on the formation of cAMP in glomeruli and proximal tubules and suggest that the greater inhibitory effect on glomerular cAMP formation in SHR may reflect an increase in alpha 2-adrenoceptor density in SHR kidneys.

Animals↗
PubMed1992

Effect of dietary sodium on platelet alpha 2-adrenoceptors in young normotensive men with or without a family history of hypertension.

OBJECTIVE: To study the effects of genetics on the response of platelet alpha 2-adrenoceptors to a change in salt intake. METHODS: Biochemical measurements and radioligand binding assays in platelets were performed in 11 normotensive male university students with a family history of essential hypertension (FH+) and in 17 students without a family history of hypertension (FH-). The 28 students were fed a high-sodium diet for 7 days and a low-sodium diet for 7 days. RESULTS: In FH+ subjects the number of alpha 2-adrenergic receptors on platelet membrane fractions increased significantly from the high-sodium diet to the low-sodium diet, even though plasma noradrenaline concentrations tended to increase with the low-sodium diet. There was no change in the number of alpha 2-adrenoceptors in the FH--group. In both groups the radioligand binding affinity was decreased during a low-sodium period compared with in a high-sodium period. CONCLUSION: In the FH+ subjects the change in platelet alpha 2-adrenoceptors associated with altered sodium status was similar to that seen in patients with salt-sensitive hypertension, suggesting that there is a genetic susceptibility to sodium.

Adult↗
PubMed1992

[Adenosine and adenosine receptors in the kidney].

In the kidney, adenosine plays important regulatory roles, including renal blood flow, glomerular filtration rate, renin secretion, tubuloglomerular feedback, tubular reabsorption of sodium and water, sympathetic neurotransmitter release, and erythropoietin secretion. These functions are mediated through adenosine 1 (A1)-receptors and adenosine 2 (A2)-receptors. These receptors couple to the inhibition and stimulation of adenylate cyclase, through Gi and Gs proteins, respectively. A variety of other effecter systems have been reported to be coupled to A1 receptors, including phospholipase C, phospholipase A2 and potassium, as well as Ca++ channels. Recently, A1 receptors, A2 receptors and novel A2 receptor have been cloned, sequenced and expressed. In association with the development of selective adenosine analogues, we are now ready to take up problems at the biochemical and molecular biological levels.

Adenosine↗
PubMed1989

Participation of the sympathetic nervous system in hypertension in rats with subtotal renal ablation.

To clarify the role of the sympathetic nervous system in the development of hypertension in chronic renal failure, plasma levels and urinary excretions of catecholamines were evaluated in male Sprague-Dawley rats. The renal mass of the rats was reduced by removing one kidney and two-thirds of the contralateral kidney (5/6 nephrectomy). Five-sixths nephrectomy was followed by significant increases in serum creatinine (to 0.55 +/- 0.03 mg/dl) and urea nitrogen (to 42.9 +/- 3.8 mg/dl). There was a concomitant increase in mean blood pressure, measured directly by an implanted aortic catheter, in comparison with control rats (155.3 +/- 8.3 versus 123.6 +/- 3.3 mmHg, P less than 0.01). Both plasma levels and urinary excretion of norepinephrine and epinephrine were elevated in the 5/6-nephrectomized rats compared with controls. Mean blood pressure correlated negatively with 24-h creatinine clearance (r = -0.66, P less than 0.05), and positively with plasma norepinephrine (r = 0.83, P less than 0.01) and urinary excretion of norepinephrine (r = 0.63, P less than 0.05). These results suggest that not only the decrease in renal function, but also hyperactivity of the sympathetic nervous system, may be involved in the pathogenesis of hypertension in rats with subtotal renal ablation.

Animals↗
PubMed1989

Changes of the serum amikacin (AMK) level in patients with serious acute renal failure treated by continuous arteriovenous hemofiltration (CAVH).

This study clarified changes in the serum amikacin (AMK) levels in the blood of 5 patients (4 men and 1 woman; average age 59.2 +/- 5.9 years) with serious acute renal failure treated by continuous arteriovenous hemofiltration (CAVH). The following principal results were obtained. (A) The average remaining rate of AMK in the blood after 6 h was 60.8 +/- 5.3% and 50.4 +/- 5.3% after 12 h. The average half-life period (t1/2 beta) of AMK in the blood during CAVH was 18.3 +/- 3.4 h. (B) The remaining rate of AMK in the blood after 12 h correlated significantly with the blood urea nitrogen (BUN) level (r = 0.71, p less than 0.05) and with the volume of urine excreted per day (r = -0.71, p less than 0.05). (C) The average lowest AMK concentration after 24 h for a continuous 17-day period was 3.3 micrograms/ml. These results suggest that the administration of 100 mg of AMK once a day is useful and safe for patients with serious acute renal failure treated by CAVH and that it will not accumulate in the body.

Acute Kidney Injury↗
PubMed1989

Effect of sodium restriction on platelet function in patients with essential hypertension.

The effects of sodium intake on blood pressure and platelet function were evaluated in 19 subjects with essential hypertension (10 men and 9 women; mean age 49.7 years). The study was conducted under 3 conditions: (1) normal sodium diet (12 g/day of salt was used in cooking), (2) after 5 days of mild sodium restriction diet (6 g/day of salt was used in cooking) and (3) after moderate sodium restriction (no salt was used in cooking). Blood pressure was significantly reduced following sodium restriction without any change in heart rate. The ratio of the plasma level of beta-thromboglobulin to platelet factor IV, regarded as the most reliable index for platelet activation in vivo, increased significantly after mild sodium restriction; this change was maintained after moderate sodium restriction. Plasma thromboxane B2, a stable metabolite of thromboxane A2, increased significantly after sodium restriction; the level of 6-ketoprostaglandin F1 alpha, a stable metabolite of prostacyclin, was unaffected. These results indicate that dietary sodium restriction induces both a reduction of blood pressure and an activation of platelet function in vivo. Thus, one must consider both antihypertensive effects and effects on platelet function as factors in adjusting the dietary sodium intake in the course of antihypertensive therapy.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effect of sodium intake on the hypotensive effect of calcium antagonists.

To clarify the influence of Na balance on the hypotensive effect of calcium antagonists, the changes of blood pressure and humoral factors after a single oral administration of 40 mg nicardipine were evaluated in 15 subjects with essential hypertension under high, normal, and low Na regimens (mean 24 hour urinary Na excretion: 320 +/- 24, 147 +/- 7, 27 +/- 6 mEq, respectively). Nicardipine induced a significant reduction of mean blood pressure and increase in heart rate. The change of mean blood pressure after nicardipine was negatively related to the pretreatment mean blood pressure under the three levels of Na intake (p less than 0.01). The slopes of the correlation lines for high, normal, and low Na regimens were -0.61, -0.69, and -0.52, respectively, without statistical significance. Nicardipine brought about significant increases in plasma renin activity and plasma norepinephrine, but no changes in plasma levels of epinephrine, 6-keto-prostaglandin F1 alpha, thromboxane B2 or serum aldosterone concentration. These results suggest that the magnitude of the untreated blood pressure and thereby the peripheral resistance are major determinants of the blood pressure fall caused by calcium antagonists, and that the failure to increase aldosterone and epinephrine in the face of peripheral vasodilation may be responsible in part for the hypotensive effect of this drug.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Alpha 2-adrenoceptor stimulation inhibits cellular cyclic AMP production in microdissected human glomeruli.

The physiological role of numerically predominant alpha 2-adrenoceptor in the kidney is still unknown. This study examined the effect of alpha 2-adrenoceptor stimulation on the production of cAMP from isolated human glomeruli. Unaffected portions of human kidneys which had been removed because of renal cell carcinoma were used for the study. Glomeruli were dissected manually under a stereo microscope. In these glomeruli, alpha 2-adrenoceptor stimulation with epinephrine in the presence of propranolol inhibited significantly parathyroid hormone-dependent increases in cAMP production. This inhibitory effect of epinephrine was removed by adding a specific alpha 2-adrenoceptor antagonist, yohimbine, indicating that the inhibitory effect of epinephrine on cAMP formation was due to alpha 2-adrenoceptor stimulation. Thus, alpha 2-adrenoceptors are involved in the inhibition of cAMP production in human glomeruli.

Cyclic AMP↗
PubMed1989

Inhibitory effect of human atrial natriuretic peptide on cyclic AMP levels in microdissected human glomeruli.

We studied whether alpha-human atrial natriuretic peptide (alpha-hANP) had the capacity to regulate cyclic AMP (cAMP) levels in human glomeruli, since decreased cAMP in the glomerulus may increase the glomerular filtration rate (GFR) through increasing kf (glomerular capillary ultrafiltration coefficient). Human kidneys were obtained at surgery for carcinoma. Normal cortical tissues from these kidneys were used for the study. After incubating the renal cortical slices with 0.1% collagenase, glomeruli were dissected manually under the stereomicroscope. Two glomeruli were incubated (37 degrees C, 2 min) with parathyroid hormone (PTH) and/or alpha-hANP. cAMP was determined by radioimmunoassay. alpha-hANP at a concentration of 5 x 10(-6) M had no effect on glomerular cAMP accumulation in the basal condition. PTH stimulated cAMP formation in a dose-dependent manner. alpha-hANP inhibited significantly the increase in cAMP formation induced by PTH (p less than 0.01). This action of alpha-hANP was dose-dependent, with a maximum of 50% inhibition. PTH is one of the endogenous substances that are known to increase cAMP formation and decrease kf. Thus, it seems likely that alpha-hANP increased GFR through modulating the production of cAMP in human kidney.

Atrial Natriuretic Factor↗
PubMed1987

Identification of an atrial natriuretic peptide specific receptor in human kidney.

A specific receptor for human atrial natriuretic peptide (h-ANP) was identified in the human kidney using the radioligand binding assay. Samples were prepared from non-malignant renal tissues obtained at nephrectomy of patients with renal carcinoma. Binding studies using [125I]hANP were performed at 0 degree C for 20 minutes and terminated by a rapid filtration technique. Scatchard plot analysis revealed [125I]hANP bound to a single class of binding site (Kd = 0.4 +/- 0.2 nM) with a density of 16 +/- 4 fmol/mg protein in the renal cortex (n = 7). The binding was rapid and maximal binding was obtained within 20 minutes after the start of incubation. Radioligand displacement was observed in a dose dependent fashion when cold hANP was entered into the reaction mixture. However, unrelated agents, such as angiotensin II or 1-epinephrine, did not affect the binding. This is the first time characterization of the hANP receptor in the human kidney has been conducted using a Scatchard plot analysis.

Atrial Natriuretic Factor↗
PubMed1987

[Fundamental and clinical studies of flomoxef in the pediatric field].

Fundamental and clinical studies of flomoxef (FMOX, 6315-S) were conducted and the obtained results are summarized as follows. For the pharmacokinetic investigation, FMOX at 10 or 20 mg/kg was administered by intravenous drip infusion over 30 minutes. In the 10 mg/kg group, the maximum blood concentration was reached just after completion of the drip infusion with the mean concentration of 30.3 +/- 4.5 micrograms/ml, and the mean half-life was 0.734 +/- 0.196 hour. The 6-hour urinary excretion rate was 72.3%. In the 20 mg/kg group, which also showed the peak concentration immediately after completion of the drip infusion, the mean peak blood concentration was 54.3 +/- 9.7 micrograms/ml and the mean half-life was 0.628 +/- 0.185 hour. The 6-hour urinary excretion rate was 69.3%. The urinary recovery tended to be lower in children than in adults. Between 10 mg/kg and 20 mg/kg, a definite correlation was observed between dose levels and blood concentrations. In the clinical investigation conducted with a total of 30 patients (22 with respiratory tract infection, 3 with lymphadenitis, 2 each with urinary tract infection and cellulitis, and 1 with acute osteomyelitis), FMOX was found to be excellent in 14 cases, good in 9, fair in 1, poor in 1, and not evaluable in 5. The efficacy rate was, therefore, 92.0%. In the bacteriological evaluation, 8 out of 12 clinically isolated strains were eradicated, 2 unchanged and 2 unknown. The elimination rate was 80.0%. Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, eosinophilia, prolongation of APTT, increased platelet count, and a slight elevation of GOT were observed.

Adolescent↗
PubMed1986

Existence of renal alpha 1- and alpha 2-adrenoceptors in the human kidney: radioligand binding study in membranes from the human renal cortex and medulla.

We investigated alpha 1- and alpha 2-adrenoceptors by radioligand binding studies in plasma membranes from the human renal cortex and medulla using a new alpha 1-adrenoceptor antagonist, 3H-bunazosin, and an alpha 2-adrenoceptor antagonist, 3H-rauwolscine. Human kidneys were obtained post-mortem (n = 4) or at surgery for carcinoma of the kidney (n = 10). The specific binding of both radioligands was rapid, saturable, reversible and specific. Scatchard analysis of 3H-bunazosin binding showed that the renal cortex had a KD of 4.6 nmol/l and a Bmax of 34.7 fmol/mg of protein, and the medulla a KD of 2.4 nmol/l and a Bmax of 23.2 fmol/mg. The specific binding of 3H-rauwolscine had a KD of 5.6 nmol/l and Bmax of 22.4 fmol/mg of protein for the cortex and values of 5.1 and 42.0, respectively, for the medulla. Competitive inhibition studies suggested that the binding of both radioligands was to sites with alpha 1 and alpha 2 specificity, respectively. The present studies demonstrate that human renal plasma membranes from both the cortex and medulla contain binding sites with both alpha 1- and alpha 2-adrenoceptors.

Humans↗