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Biomedical subjects

N Murayama

Publications and source records attributed to N Murayama.

At least 181 records · Page 10Linked to original sources
PubMed1985

Localization of thyroxine 5'-monodeiodinase activity in the renal proximal tubules in rabbits and rats.

To determine the localization of T4 5'-monodeiodinase activity in rabbit and rat nephron segments, the formation of tri-iodothyronine (T3) from thyroxine (T4) was measured in kidney homogenate and in isolated nephron segments obtained by the microdissection method. In order of decreasing activity, homogenates of rabbit renal cortex, outer medulla and inner medulla were capable of converting T4 to T3. In the isolated nephron segments of the rabbit cortex, the activities were noted in both proximal convoluted and proximal straight tubules. On the other hand, the activities were not detected in segments including the cortical thick ascending limb of Henle's loop, the distal convoluted tubule, the connecting tubule, and the cortical collecting tubule. It is concluded that both the convoluted and the straight tubules are the sites of T3 production in the kidney.

Animals↗
PubMed1985

Effects of calcium on the vasopressin-sensitive cAMP metabolism in medullary tubules.

The modulatory effect of Ca on [Arg8]vasopressin-dependent (AVP) cAMP metabolism was studied in medullary collecting tubules (MCT) and medullary ascending limbs (MAL) microdissected from rat kidney. In MCT segments incubated in vitro with AVP, the accumulation of cAMP was enhanced (delta +59%) when Ca was omitted from the incubation medium compared with a medium with 2 mM of ionized calcium (Ca2+). Ionophore A23187 caused a decrease in AVP-stimulated cAMP accumulation in MCT in the presence of 2 mM Ca2+ but not in a Ca2+-free medium. Diltiazem and verapamil enhanced the AVP-stimulated cAMP accumulation in MCT; PTH had no detectable effect. A23187 caused a dose-dependent inhibition of cAMP accumulation stimulated by AVP with forskolin in both MCT and in MAL. However, in MAL the A23187 concentration needed for half-maximum inhibition (6.3 X 10(-6) M) was higher than for MCT (3.9 X 10(-7) M). The maximum inhibition in MAL (-65%) was less than in MCT (-97%). In the presence of 3-isobutyl-1-methylxanthine, AVP-stimulated cAMP accumulation was inhibited by A23187 in MCT (-45%) but not in MAL. Naproxen or ibuprofen did not relieve the inhibitory action of A23187 in MCT. Added Ca2+ inhibited the AVP-stimulated adenylate cyclase in MCT and MAL (half-maximum approximately equal to 5 X 10(-4) M Ca2+) and stimulated cAMP phosphodiesterase (cAMP-PDIE) in both MCT and in MAL (half-maximum approximately equal to 9 X 10(-5) M Ca2+). Incubation of MCT and MAL with A23187 decreased (-50%) the content of ATP. Results suggest that increased influx of extracellular Ca2+ inhibits the AVP-stimulated cAMP accumulation in MCT and to a much lesser degree in MAL. Deceased cAMP accumulation in MCT is probably due to both stimulation of cAMP-PDIE and the inhibition of adenylate cyclase, whereas in MAL it is due to stimulation of cAMP-PDIE. The results suggest that Ca2+ influx exhibits a negative modulatory effect on AVP-dependent cAMP metabolism mainly in MCT.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Hypergastrinemia and achlorhydria in chronic renal failure.

In 68 patients with chronic renal failure (CRF), 15 patients with duodenal ulcer and 15 normal subjects, basal plasma gastrin levels and basal and stimulated gastric acid secretion were measured. Two antisera were used: antiserum R2702 with specificity for human G34 and its N-terminal fragments [G34] and antiserum 2604 with specificity for the four main components of gastrin (total gastrin). Basal gastrin concentrations of both total gastrin and G34-like immunoreactivity (G34LI) were significantly higher in the CRF patients than in the other two groups, irrespective of dialysis. Total gastrin levels were not correlated with serum creatinine levels. Total gastrin levels were significantly decreased during hemodialysis, but G34LI levels showed no significant change. A small amount of total gastrin was detected in the dialysate by antiserum 2604. As to the postprandial gastrin release, in the first 30 min, the pattern of response in the patients with CRF was similar to that of the normal subjects, but the peak value was attained later, and the response was more rather prolonged. Gastric analysis showed a low basal acid out put and impaired acid secretion in response to secretagogue. It is concluded that (1) one of the predominant circulating forms of gastrin in CRF is G34LI, and (2) the hypergastrinemia in the CRF patients is probably due to reduced removal of gastrin by kidneys, increased gastrin production by impairment of the negative acid feedback mechanism induced by parietal cell dysfunction or reduced parietal cell sensitivity to gastrin by atrophic gastritis.

Achlorhydria↗
PubMed1985

Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats.

A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study to clarify the mechanism by which Li administered orally for several weeks induces polyuria and NDI in rats. Albino rats consuming a diet which contained Li (60 mmol/kg) for 4 wk developed marked polyuria and polydipsia; at the end of 4 wk the plasma Li was 0.7 +/- 0.09 mM (mean +/- SEM; n = 36). Li-treated rats had a significantly decreased (-33%) tissue osmolality in papilla and greatly reduced cortico-papillary gradient of urea (cortex--43%; medulla--64%; papilla--74%). Plasma urea was significantly (P less than 0.001) lower in Li-treated rats (5.4 +/- 0.2 mM) compared with controls (6.8 +/- 0.3 mM). Medullary collecting tubules (MCT) and papillary collecting ducts (PCD) microdissected from Li-treated animals had higher content of protein than MCT and PCD from the control rats. The cAMP accumulation in response to AVP added in vitro was significantly (delta = -60%) reduced. Also, the cAMP accumulation in MCT and PCD after incubation with forskolin was markedly lower in Li-treated rats. Addition of 0.5 mM 1-methyl,3-isobutyl-xanthine did not restore the cAMP accumulation in response to AVP and forskolin in MCT from Li-treated animals. In collecting tubule segments from polyuric rats with hypothalamic diabetes insipidus (Brattleboro homozygotes) the AVP-dependent cAMP accumulation was not diminished. The activity of adenylate cyclase (AdC) in MCT of Li-treated rats, both the basal and the activity stimulated by AVP, forskolin, or fluoride, was significantly (delta approximately equal to -30%) reduced, while the activity of cAMP phosphodiesterase (cAMP-PDIE) in the same segment showed no significant difference from the controls. Also, the content of ATP in MCT microdissected from Li-treated rats and incubated in vitro did not differ from controls. The rate of [14C]succinate oxidation to 14CO2 in MAL was inhibited (-77%) by 1 mM furosemide, which indicates that this metabolic process is coupled with NaCl cotransport in MAL. The rate of (14)CO(2) production from [14C]succinate in MAL was not significantly different between control and Li-treated rats. In MCT of control rats, the rate of [14C]succinate oxidation was approximately 3 times lower than in MAL. The rate of (14)CO(2) production from [(14)C]succinate in MCT of Li-treated rats was significantly (delta +33%) higher than in MCT dissected from control rats. Based on these results, we conclude that at least two factors play an important role in the pathogenesis of NDI consequent to chronic oral administration of Li: (a) decreased ability of MCT and PCD to generate and accumulate cAMP in response to stimulation by AVP; this defect is primarily due to diminished activity of AdC in these tubular segments caused by prolonged exposure to Li; and (b) lower osmolality of renal papillary tissue, due to primarily to depletion of urea, which decreases osmotic driving force for water reabsorption in collecting tubules. On the other hand, NaCI reabsorption in MAL is apparently not affected by chronic Li treatment.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Evidence for beta adrenoceptors in proximal tubules. Isoproterenol-sensitive adenylate cyclase in pars recta of canine nephron.

Observations in vivo suggest that catecholamines modulate reabsorptive functions of proximal tubules by acting on beta-adrenoceptors. However, beta-catecholamine binding sites or beta-adrenoceptor-sensitive adenylate cyclase (AdC) has not been found in segments of proximal tubules of rat, rabbit, or mouse kidney. In the present study, we investigated the responsiveness of AdC to catecholamines, [8-Arg]vasopressin (AVP), and to parathyroid hormone (PTH) in proximal convoluted tubules (PCT), proximal straight tubules (PST), and in late distal convoluted tubules (LDCT) microdissected from canine kidney. Isoproterenol (ISO) caused a marked and dose-dependent stimulation of AdC in PST (maximum: delta + 850%; half maximum stimulation at 10(-7) M ISO), but ISO had no effect on AdC in PCT. The AdC in both PCT and PST was markedly stimulated by PTH; AVP stimulated the AdC in LDCT but not in PST or in PCT. The stimulatory effect of 10(-5) M ISO in PST (delta + 725%) was significantly greater than in LDCT (delta + 307%); norepinephrine and epinephrine had stimulatory effects in PST similar to ISO. The stimulation of AdC in PST by ISO was blocked by propranolol and by beta 2-blocker ICI-118551. On the other hand, alpha-blocker phentolamine and beta 1-blocker metoprolol did not abolish the stimulation of AdC in PST by ISO. The accumulation of cAMP in intact PCT and PST incubated in vitro was stimulated by PTH both in PST and in PCT, but ISO elevated cAMP (delta + 683%) only in PST. Our results show that proximal tubules of canine nephron, PST but not PCT, contain beta-adrenoceptors of beta 2 subtype coupled to AdC. These observations provide direct evidence that the effects of catecholamines, either released from renal nerve endings or arriving from blood supply, can act directly on beta 2-adrenoceptors located in proximal tubules, and also suggest that at least some of the catecholamine effects in proximal tubules are mediated via cAMP generation.

Adenylyl Cyclases↗
PubMed1985

Modulatory effect of thyroid hormones on uptake of phosphate and other solutes across luminal brush border membrane of kidney cortex.

The mechanism whereby thyroid hormones modulate the transport properties of luminal brush border membrane (BBM) of renal proximal tubules was studied in thyroparathyroidectomized rats. Administration of both T4 and T3 increased BBM capacity for Na+ gradient-dependent uptake of phosphate (Pi) by BBM vesicles (BBMV). This effect of thyroid hormones was present in thyroparathyroidectomized and hypophysectomized rats, and it was not blocked by a saturating dose of propranolol. The stimulatory effect of T3 and T4 on BBM transport of Pi was dose dependent in the range of 5.2-520 nmol/100 g BW. Pretreatment of rats with inhibitors of 5'-monodeiodinase (5'-DI), iopanoic acid or ipodate, prevented the increase in serum T3 in rats injected with T4, but it did not diminish the increase in BBM transport of Pi. Administration of iopanoic acid and ipodate also prevented a 5-fold increase in 5'-DI activity in renal cortical tissue elicited by T4 administration. Treatment with T3 resulted in an increase of Pi transport across BBM from kidneys of rats subjected to dietary Pi deprivation due either to total fasting or to feeding of a low Pi diet. Further, T3 administration enhanced amiloride-sensitive Na+-H+ countertransport across BBM, but the uptake of 22Na+ by BBMV in the absence of pH gradient was not changed. The Na+ gradient-dependent uptake of L-[3H]proline by BBMV was slightly decreased, but the uptake of [14C]citrate was not changed in response to T3. Administration of T3 increased Pi transport in BBMV prepared from juxtamedullary cortex, but not in BBMV from superficial cortex. Conversely, the rate of Na+-H+ countertransport was enhanced, and the enzymatic activity of alkaline phosphatase was decreased in BBMV from superficial cortex; no changes in these parameters were found in BBMV from juxtamedullary cortex. Our results indicate that the stimulatory effect of administered T3 and/or T4 on renal BBM transport of Pi is distinct from the modulatory effect of dietary Pi intake and is not secondary to the beta-effect of catecholamines or to altered secretion of GH. Both T3 and T4 elicit the increase in BBM transport of Pi in a similar manner; T4 is effective even after profound inhibition of in vivo conversion of T4 to T3 by potent 5'-DI inhibitors. Administration of T3 stimulates Na+ gradient-dependent Pi uptake only in BBMV prepared from the juxtamedullary zone, and it stimulates the H+-Na+ countertransport only in BBMV from the outer cortical zone. These findings indicate that thyroid hormones modulate the two distinct transport functions of BBM derived from two different populations of renal proximal tubules.

Animals↗
PubMed1985

The vasopressin-sensitive adenylate cyclase in collecting tubules and in thick ascending limb of Henle's loop of human and canine kidney.

The major tubular effects of [8-Arg]vasopressin (AVP) in regulation of renal water excretion are initiated by stimulation of adenylate cyclase (AdC) coupled with V2 receptors. We explored whether the AVP-sensitive AdC is present in both collecting tubules and the thick ascending limb of Henle's loop of human and canine kidney. In cortical collecting tubule (CCT) and medullary collecting tubules (MCT) of human kidney, AdC was markedly stimulated by AVP [maximum change from basal level (delta), +2700%] and the the nonhormonal stimulatory agent forskolin (delta, +2000%). In human CCT, the effects of both compounds were synergistic. In contrast, AVP had no effect on AdC in either the medullary (MAL) or cortical (CAL) segment of the thick ascending limb of Henle's loop of human kidney; AVP also did not stimulate AdC in CAL or MAL in the presence of forskolin. Similar to that in the human kidney, in the canine kidney, AdC in CCT and MCT was markedly stimulated by AVP and forskolin (delta, +1000%), but AVP had no effect on AdC in CAL and MAL of the canine kidney. In intact tubules dissected from dog kidney and incubated in vitro, AVP markedly increased cAMP accumulation in MCT. AVP also elicited a small but detectable increase in cAMP accumulation in MAL. From these observations, we conclude that AVP-sensitive AdC is well developed in collecting tubules, but that AVP-sensitive AdC is absent in MAL and CAL of human kidney. Likewise, in canine nephron, the AVP-sensitive AdC of MAL and CAL is rudimentary or very labile. These findings suggest that the unresponsiveness of the AdC-cAMP system to AVP in segments of the thick ascending limb of Henle's loop may be a factor that accounts for a relatively low maximum osmotic concentration of urine which can be achieved by human or canine kidneys.

Adenylyl Cyclases↗
PubMed1985

[Correlation of subjective assessments with somatosensory evoked potentials to electrical stimulation of the finger in man].

The relationship between 5 positive components of somatosensory evoked potentials (EPs) and subjective response to electrical stimuli, which were recorded in the same human subjects, was assessed in the present study. Five levels of tactile stimuli and 6 levels of noxious stimuli were applied to the tip of the right index finger. The relationship between the magnitude of subjective response and stimulus intensity was well expressed by a power function. Of 5 major positive components in an EP, P30 and P50 were localized at contralateral primary somatic projection area, while P90, P190 and P270 were at the vertex area. The amplitude of the 5 components systematically increased as increasing stimulus intensity, and also increased with the magnitude of subjective response. A significant correlation between the amplitude of P30 or P50 and stimulus intensity was found when the effect of subjective response was partially out. By contrast, the amplitudes of P190 and P270 were associated with subjective response when the effect of stimulus intensity was partially out. These results suggest that the earlier EP components reflect sensory signal processing, while the latter ones concern the subjective evaluating system.

Adult↗
PubMed1985

[Somatosensory evoked potentials and pain discrimination in man].

The relationship between 10 components of somatosensory evoked potentials (EPs) and pain discrimination in man was studied using Signal Detection Theory (SDT) psychophysics. Two painful electrical stimuli were delivered to the right index finger in random order over all trials. EPs were recorded from the scalp at the contralateral primary somatic projection area while subjects performed SDT discrimination. The stimulus-response combination was classified into 4 categories according to SDT response: hits, misses, false alarms (FAs) and correct rejections (CRs). The amplitudes and peak latencies of EPs in 4 categories were compared with each other. EPs associated with hits and FAs had significantly greater amplitude at P 190, N 220 and P 270 than those associated with misses and CRs, while there was no change in the amplitude of other components. The amplitude of these 3 components systematically increased with an increase in the magnitude of subjective response. Peak latencies of all components were not related to the response categories. These results indicate that the amplitude of the 3 last components may be concerned with the pain evaluating system in the brain.

Adult↗
PubMed1984

Self-adaptive modification of red-cell membrane lipids in lecithin: cholesterol acyltransferase deficiency. Lipid analysis and spin labeling.

In a patient with lecithin: cholesterol acyltransferase deficiency, free cholesterol was markedly increased, and esterified cholesterol was diminished. In the patient's plasma, an increase in phosphatidylcholine (PC) and a decrease in sphingomyelin were observed. Concomitantly, an increase in a shorter acyl chain 16:0 was noted in PC, sphingomyelin and phosphatidylethanolamine (PE). In contrast to these results, longer chains such as 22:0 and 24:0 were decreased, especially in sphingomyelin. Unsaturated double bonds such as 18:1 was also increased in PC and PE. In the red-cell membrane lipids, the increase in free cholesterol was counteracted by an increase in PC and by a decrease in sphingomyelin and PE, reflecting changes in the patient's plasma lipids. Increased 16:0 (in PC) and decreased 18:0 and 24:0 were observed. The increased plasma free cholesterol due to metabolic defect (lecithin: cholesterol acyltransferase deficiency) led to decreased red-cell membrane fluidity. This effect appeared to be counteracted by changing phospholipid composition (increased PC and decreased sphingomyelin and PE), by increasing shorter chains (16:0), by decreasing longer chains (18:0 and 24:0) and by increasing unsaturated double bonds (18:2). These results can be interpreted as a self-adaptive modification of lecithin: cholesterol acyltransferase deficiency-induced red-cell membrane abnormalities, to maintain normal membrane fluidity. This speculation was supported by the ESR spin-label studies on the patient's membrane lipids. The normal order parameters in intact red cells and in total lipid liposomes were decreased if cholesterol-depleted membrane liposomes were prepared. Thus, the hardening effect of cholesterol appeared to be counteracted by the softening effects described above. Overall membrane fluidity in intact red cells of the lecithin: cholesterol acyltransferase-deficient patient was maintained normally, judged by order parameters in ESR spin-label studies.

Cholesterol↗
PubMed1984

Decreased sodium influx and abnormal red cell membrane lipids in a patient with familial plasma lecithin: cholesterol acyltransferase deficiency.

Red cell membrane metabolism in familial lecithin:cholesterol acyltransferase (LCAT) deficiency was investigated. The family presented here is the third case discovered in Japan. An increase of free cholesterol was observed in the red cell membranes, concomitant with increased phosphatidyl choline. Osmotic fragility of the patient's red cells was diminished rather than increased. Red cell survival (51Cr T1/2) was shortened (15 days). Sodium influx was markedly decreased, although sodium efflux, both ouabain-sensitive and ouabain-insensitive, was normal. The activity of acetyl-cholinesterase as a marker of the outer leaflet of the red cell membranes was decreased, while the activity of glyceraldehyde-3-phosphate dehydrogenase as a marker of the inner leaflet was normal. No abnormalities of adenosine triphosphatases in red cell membranes were observed. These results suggest that the alteration of cholesterol metabolism in the plasma of LCAT deficiency increases the red cell membrane cholesterol and affects the functions of the red cell membranes, especially of the outer leaflet, which may result in decreased sodium influx.

Blood Transfusion↗
PubMed1984

Effects of plasma infusion on plasma lipids, apoproteins and plasma enzyme activities in familial lecithin: cholesterol acyltransferase deficiency.

The siblings presented here are the third family found in Japan with familial LCAT deficiency. Their post-heparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured selectively by an immunochemical method. Plasma triglyceride levels were elevated, and post-heparin plasma lipoprotein lipase was decreased only in a patient with nephropathy, while hepatic triglyceride lipase activities were within reference limits in both patients. The plasma concentrations of apo A-I, apo A-II, and apo B were reduced in both patients. On the other hand, the plasma concentration of apo E was markedly increased. Enzyme replacement therapy by plasma transfusion in the propositus resulted in marked improvement of deranged compositions of triglyceride-rich lipoproteins. Also, improvement of the plasma apo E concentration was demonstrated, while the improvement of post-heparin lipase did not occur. These results suggest that LCAT may play an important physiological role in triglyceride metabolism as well as in cholesterol metabolism.

Apoproteins↗