Search PubMed⌕ Search

Biomedical subjects

T Terasaki

Publications and source records attributed to T Terasaki.

At least 145 records · Page 8Linked to original sources
PubMed1990

Specific binding and clearance of [3H]dynorphin (1-13) in the perfused rat lung: an application of the multiple-indicator dilution method.

The clearance and binding of a kappa-selective opioid peptide, dynorphin (1-13), in the perfused rat lung has been examined, using the multiple indicator dilution method. More than 50% of [3H]dynorphin (1-13) entering the pulmonary circulation was eliminated by the lung during a single passage of a tracer dose. By contrast, when a high dose (100 microM) of dynorphin (1-13) was concomitantly injected, [3H]dynorphin (1-13) behaved like [14C]sucrose, an extracellular marker. The kinetic analyses of the pulmonary venous outflow curves of [3H]dynorphin (1-13) and [14C]sucrose at low and high doses of dynorphin (1-13) indicated that the initial uptake rate constant, extraction ratio and distribution volume of [3H]dynorphin (1-13) decreased significantly in the presence of a high concentration of unlabelled dynorphin (1-13). These results suggest that [3H]dynorphin (1-13) is eliminated by a saturable process and binds to a specific binding site in the perfused lung, which may be the kappa-type binding site. The multiple indicator dilution technique, in combination with a moment analysis, was successfully applied to demonstrate the specific binding and clearance of dynorphin (1-13) in the perfused lung.

Analgesics↗
PubMed1990

Dysfunction of choline transport system through blood-brain barrier in stroke-prone spontaneously hypertensive rats.

The blood-brain barrier (BBB) transport of choline was compared between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar KY rats (WKY). The permeability surface area product (PS) of [3H]choline through the BBB in SHRSP (3.03 X 10(-3) +/- 1.09 X 10(-3) ml/min/g brain) was significantly lower than that in WKY (7.23 X 10(-3) +/- 0.97 X 10(-3) ml/min/g brain) in the presence of respective rat sera. No significant difference in the brain vascular space was indicated from the apparent uptake of [3H]sucrose between SHRSP and SKY. There was no significant difference for the Michaelis constant of choline transport between SHRSP (262 +/- 97 microM) and WKY (180 +/- 32 microM). However, the maximum velocity in SHRSP (3.41 +/- 1.19 nmol/min/g brain) was 37% lower than in WKY (5.40 +/- 0.38 nmol/min/g brain). Brain microdialysis technique was employed to collect the brain interstitial fluid in the rat hippocampus. The concentration of free choline in the brain dialysate in SHRSP was about half of that in WKY, while no significant difference was observed for the plasma concentration of free choline between SHRSP and WKY. In contrast, no significant difference was observed for the transport of D-[3H]glucose, 3-methyl-[3H]D-glucose and [3H]-phenylalanine through the BBB between SHRSP and WKY. Accordingly, the decreased choline concentration in the brain interstitial fluid ascribed to the specific dysfunction of the BBB choline transport has been demonstrated in SHRSP.

3-O-Methylglucose↗
PubMed1990

Acidic drug transport in vivo through the blood-brain barrier. A role of the transport carrier for monocarboxylic acids.

The relationship of the transports between acidic drugs and monocarboxylic acids through the blood-brain barrier (BBB) was examined using the carotid artery injection technique in rats. The BBB uptakes of [3H]acetic acid and [14C]salicylic acid were significantly reduced by the presence of the respective unlabeled compounds, valproic acid, lactic acid, benzoic acid, nicotinic acid or beta-lactam antibiotics (benzylpenicillin, propicillin and cefazolin), but was not reduced by choline, phenylalanine and a basic drug, eperisone. A remarkable pH dependency was observed for the BBB uptake of [14C]salicylic acid at the pH region of 4.0 to 7.4. Interestingly, 10 mM of salicylic acid diminished significantly the pH dependent BBB uptake of [14C]salicylic acid. Similar results were obtained in the BBB uptake of [14C]nicotinic acid. No significant difference was observed in the transport of monocarboxylic acids through the BBB between normotensive Wistar KY rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). From these observations, acidic drugs could be transported by a carrier-mediated system for monocarboxylic acids at the BBB and the transport system was not changed by the disease state.

Acetates↗
PubMed1990

Sodium and pH dependent carrier-mediated transport of antibiotic, fosfomycin, in the rat intestinal brush-border membrane.

The mechanism of intestinal absorption of an antimicrobial agent, fosfomycin (FOM), was investigated in rats using small intestinal brush-border membrane vesicles (BBMV). The uptake of [3H]FOM by BBMV was osmolarity- and temperature-sensitive and showed apparently saturable uptake kinetics consistent with the Michaelis-Menten equation, having Kt = 15.3 mM and Jmax = 7.78 nmol/30 s/mg protein at 37 degrees C. An overshoot uptake of FOM was observed in the presence of an inwardly direct Na+ gradient. The replacement of extravesicular Na+ with choline or mannitol significantly reduced the uptake. An addition of a protonophore, FCCP, significantly decreased the initial uptake of FOM in the absence of Na+ gradient but in the presence of a H+ gradient (pHin = 7.5, pHout = 6.0), whereas in the absence of a H+ gradient no significant difference was observed between the uptakes at an acidic pH (pHin = pHout = 6.0) and a neutral pH (pHin = pHout = 7.5). An inside negative potassium diffusion potential induced by valinomycin enhanced significantly the uptake of FOM. The uptake of FOM in the presence of both Na(+)- and H(+)-gradients was significantly inhibited by phosphate, arsenate and phosphonoformic acid (PFA), which are specific inhibitors of phosphate transport, but not by D-glucose. Based on these results, it is concluded that FOM transport in the small intestine is partially shared with the Na(+)-phosphate cotransport system and in part occurs via a H(+)-gradient dependent carrier-mediated system.

Animals↗
PubMed1990

Carrier-mediated uptake of nicotinic acid by rat intestinal brush-border membrane vesicles and relation to monocarboxylic acid transport.

The intestinal transport of [14C]nicotinic acid was investigated at 27 degrees C by using brush-border membrane vesicles (BBMV) isolated from the rat small intestine. The osmolarity sensitive uptake by BBMV showed a remarkable overshoot phenomenon in the presence of an inward-directed H+ gradient (pHin = 7.5, pHout = 6.0). In contrast, the imposition of a Na+ gradient ([Na+]in = 0 mM, [Na+]out = 100 mM) had no stimulatory effect on the uptake of [14C]nicotinic acid. The remarkable pH-dependence of the initial uptake showing an increase of the uptake rate with decreasing the extravesicular pH disappeared completely in the presence of a structural analogue, isonicotinic acid, at pH below 6.5. In the presence of a H+ gradient, the initial uptake of [14C]nicotinic acid was saturable with the apparent Kt of 4.43 mM and Jmax of 2.55 nmol/mg protein/15 s. The uptake was increased by the imposition of an inside-positive membrane potential and was significantly inhibited by monocarboxylic acids such as benzoic acid, salicylic acid, acetic acid, propionic acid, valproic acid and L-lactic acids as well as two isomers (isonicotinic acid and picolinic acid). The uptake was not inhibited by nicotinamide, nicotinyl alcohol, D-glucose, p-aminohippuric acid, glycyl-L-proline, succinic acid and an exchange transport inhibitor. From these results it was concluded that nicotinic acid is transported through the intestinal brush-border membrane by a carrier-mediated system and the system can recognize some acidic drugs with a monocarboxylic group. The pH dependent intestinal uptake of nicotinic acid can be ascribed to the proton-coupled and active carrier-mediated transport mechanism rather than a simple diffusion of the undissociated nicotinic acid to follow a pH-partition hypothesis.

Animals↗
PubMed1990

In vivo and in vitro evidence for a common carrier mediated transport of choline and basic drugs through the blood-brain barrier.

The blood-brain barrier (BBB) transport system for choline and basic drugs was characterized by the in vivo carotid artery injection technique (Oldendorf, Brain Res., 24, 372-376, 1970) and in vitro uptake into isolated bovine brain capillaries (Pardridge et al., J. Neurochem., 44, 1178-1184, 1985). Basic drugs such as eperisone, thiamine and scopolamine significantly inhibited choline uptake by the BBB with the half inhibitory concentration, IC50 value of 1.45, 2.06, and 0.47 mM, respectively. On the contrary, the uptake of choline was not inhibited by amino acids (L-phenylalanine and L-arginine) and acidic drugs (nicotinic acid, salicylic acid and valproic acid). Choline was taken up by the isolated brain capillaries in concentration and temperature dependent manners. The uptake of choline by the isolated bovine brain capillaries was significantly inhibited by eperisone, scopolamine and thiamine in consistent with the in vivo results. Furthermore, eperisone inhibited competitively the uptake of choline with the inhibition constant, Ki value of 455 microM. According to these results it was suggested that in the BBB choline and basic drugs would share a common carrier-mediated transport system.

Animals↗
PubMed1990

Specific binding of beta-endorphin to the isolated renal basolateral membranes in vitro.

Binding of human beta-endorphin (beta-EP) to rat renal basolateral membranes was characterized using [125I]Tyr27-beta-EP ([125I]beta-EP) as a primary ligand. Ten millimolar of ethylenediaminetetra acetic acid (EDTA) completely inhibited the degradation of [125I]beta-EP in the incubation mixture at 4 degrees C, thus making it possible to quantitatively examine the [125I]beta-EP binding. The specific binding of [125I]beta-EP to the basolateral membranes was reversible and saturable, and a nonlinear least-squares regression analysis of a saturation isotherm revealed two different classes of specific binding sites. One class had an apparent dissociation constant (Kd) of 0.68 nM and a lower number of binding sites (33 fmol/mg protein), whereas the other class had a lower affinity (apparent Kd of 210 nM) and a higher number of binding sites (7.3 pmol/mg protein). Inhibition of the [125I]beta-EP binding by naloxone (10 microM) was approximately only 20%, and that by D-Ala2-D-Leu5-enkephalin (10 microM) was null, suggesting the major role of a non-opioid binding component in specific [125I]beta-EP binding to basolateral membranes. Moreover, a 50% inhibition by 10 microM of dynorphin(1-13) suggests that a certain region of the primary structure of beta-EP, excluding at least the NH2-terminal enkephalin sequence, is of particular importance for the [125I]beta-EP binding. These lines of evidence suggest the existence of two different classes of specific binding sites for beta-EP on the renal basolateral membranes, and the high-and low-affinity bindings may be attributed to opioid and non-opioid receptors, respectively, as judged by known characteristics of opioid and non-opioid receptors in other peripheral tissues.

Animals↗
PubMed1990

Duodenal mucosal hemodynamics in patients with liver cirrhosis.

Clinical studies show that patients with liver cirrhosis associated with portal hypertension have a high incidence of duodenal ulcer and duodenitis. However, little information is available concerning pathophysiological process of such duodenal diseases in liver cirrhosis. Hemodynamics of the duodenal mucosa was studied in cirrhotics with esophageal varices (68 cases) and in noncirrhotics with non-ulcer dyspepsia (37 cases) as well. In each group, hemoglobin concentration in the peripheral venous blood was measured, and mucosal hemodynamics was examined in 4 regions of the duodenum by endoscopic reflectance spectrophotometer. No significant intergroup difference was noted in the mean age or sex ratio. Hemoglobin concentration in the peripheral venous blood was significantly lower (p less than 0.01) in the cirrhotics. There were no significant intergroup differences in duodenal mucosal blood volume. However, the cirrhotics showed significantly lower oxygen saturation of hemoglobin in all regions of the duodenum (p less than 0.01). These results show that the cirrhotics with esophageal varices had relative increase in blood volume and decrease in oxygen saturation of hemoglobin in the duodenal mucosa. Such microcirculatory disturbances seem to predispose liver cirrhosis patients to duodenal injury.

Blood Volume↗
PubMed1990

[Three siblings with type 3 GM1-gangliosidosis--pathophysiology of dystonia and MRI findings].

GM1-gangliosidosis is a rare neurovisceral storage disease caused by an inherited deficiency of acid beta-galactosidase. The characteristic neurological feature of type 3 (adult or chronic) GM1-gangliosidosis is usually a slowly progressive dystonia with dysarthria due to predominant involvement of basal ganglia. About 20 adult patients with this disorder have been reported in the literature. However, there are no reports of 3 brothers with type 3 GM1-gangliosidosis, and MRI findings. Case 1 (proband): A 28-year-old man was hospitalized because of facial grimace, dysarthria, and generalized dystonia. He was born after normal pregnancy and delivery. His development was normal until 3 years of age when the difficulties of speaking and walking were noticed by his parents. These neurological abnormalities progressed slowly and facial grimace and dystonic movements occurred 7 years later. He could not walk at 22 years of age. On admission, he was bedridden with marked scoliosis and subluxation of the mandibule. The communication was possible only by pointing the words written on the board. Case 2: A 33-year-old man, elder brother of case 1, showed the similar neurological features and clinical course. Slit-lamp examination revealed corneal opacities which were located in the deep stroma. Case 3: A 33-year-old man, elder brother of case 1 or case 2. At age 10-11, he noted similar symptoms as case 1 or case 2. The severity of dystonia was milder than his brothers. A diagnosis of GM1-gangliosidosis in three patients was made on the basis of the following data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

In vivo evidence for carrier-mediated uptake of beta-lactam antibiotics through organic anion transport systems in rat kidney and liver.

The transport mechanisms of beta-lactam antibiotics in the rat kidney and liver were studied with an in vivo tissue-sampling single-injection technique using [3H]benzylpenicillin [( 3H]PCG) as a substrate. Concentration-dependent uptake of [3H]PCG was observed in the kidney, and the in vivo kinetic parameters were estimated as follows: the maximum uptake rate (Jmax) was 6.88 mumol/min/g of kidney, MIchaelis constant (Kt) was 1.39 mM and nonsaturable first-order rate constant (kd) was 0.414 ml/min/g of kidney. The uptake of [3H]PCG was inhibited by organic anions but not by organic cations. Several beta-lactam antibiotics also reduced the uptake of [3H]PCG. Furthermore, the organic anion, probenecid, and beta-lactam antibiotic, cefpiramide, showed a dose-dependent inhibitory effect. These results suggest participation of an organic anion transport system in uptake of beta-lactam antibiotics across the renal plasma membrane. Saturable uptake of [3H]PCG was also observed in the liver and Jmax, Kt and Kd were estimated to be 3.62 mumol/min/g of liver, 3.59 mM and 0.223 ml/min/g of liver, respectively. The in vivo influx rate calculated from Jmax/Kt in the liver was 1.01 ml/min/g of liver and was close to the in vitro value, 1.54 ml/min/g of liver, estimated previously from isolated hepatocytes. Although dipeptides and organic cations showed no effect on the hepatic uptake of [3H]PCG, probenecid significantly reduced its uptake. Several beta-lactam antibiotics also reduced the uptake of [3H]PCG by the liver. These features of the hepatic uptake of beta-lactam antibiotics through an organic anion transport system are in agreement with the previous results obtained in isolated hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Degradation kinetics of (+/-)-4'-ethyl-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HY-770) and structure-stability relationship among its analogues in aqueous solution.

The kinetics and pathways for degradation of (+/-)-4'-ethyl-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HY-770; 1), a newly developed muscle-relaxing agent, and its analogues were studied in aqueous solution at 50 degrees C, ionic strength 0.5 M, and pH 8.0-12.0. Compound 1 and its four analogues followed pseudo-first-order degradation kinetics at constant pH and temperature. From the analysis of the pH degradation-rate profiles, it is evident that specific hydroxide ion-catalyzed degradations of ionized and un-ionized species occur for 1 and its structural analogue, 3'-fluoro-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HN-961; 5). The hydroxide ion-catalyzed degradation of the ionized species was found to be 100 times faster than that of the un-ionized species and to be the major process at pH less than 9.0. On the contrary, 1 was extremely stable in 0.5 M HCl at 50 degrees C, suggesting that the hydronium ion-catalyzed degradation and the spontaneous degradation of the ionized species is negligible. The Arrhenius plot for the degradation of 1 at 35-50 degrees C and pH 9.0 showed that the apparent energy of activation was 22.0 kcal/mol. The degradation rates of the five structural analogues were significantly dependent on the electron withdrawing effect of the benzene substituents of the molecule.

Boric Acids↗
PubMed1989

Serum protein binding of lomefloxacin, a new antimicrobial agent, and its related quinolones.

The serum protein binding of lomefloxacin (LFLX), a new quinolone (pyridonecarboxylic acid), and its related analogues was studied by an ultrafiltration technique. The extent of binding of quinolones was independent of the concentration of quinolones below 100 micrograms/mL in rat serum; but, above this concentration, the binding decreased with increased drug concentration in the case of nalidixic acid and analogue 3. The extent of binding in rat serum differed widely among the quinolones examined [i.e., from 15% (norfloxacin) to 84% (nalidixic acid) at concentrations of 0.4-10.0 micrograms/mL]. Lomefloxacin was bound to serum proteins to the extent of 28.1, 20.1, and 20.6% in the sera of rats, dogs, and humans, respectively. The binding of nalidixic acid with rat serum albumin, which was very similar to that in rat serum, was concentration dependent. Some quinolone derivatives with a piperazinyl group or a relatively large-sized substituent at the 7-position exhibited a percentage unbound of approximately 70-80%, while some derivatives with small-sized substituents gave a low percentage unbound of 20-30%. This suggests that there is a steric effect of the substituents at the 7-position of quinolones on their binding characteristics with serum proteins. The results of the present study indicate that quinolones bind mainly with albumin among serum proteins and that the remarkable difference of the extent of binding of quinolone analogues is related to the size of the substituent at the 7-position of the molecule, possibly due to its steric effect.

Animals↗
PubMed1989

Age-related change in tissue-to-plasma partition coefficient of cefazolin for noneliminating organs in the rat.

Age-related changes in tissue distribution characteristics of cefazolin, a cephalosporin antibiotic, were examined for noneliminating organs of rats. The in vivo tissue-to-plasma partition coefficients (Kp,vivo) varied markedly among different ages and organs. In particular, muscle and skin acted as reservoirs for cefazolin distribution. There were also marked differences in interstitial fluid space (IS), determined using [14C]inulin, among different ages and organs. For muscle and bone, the magnitude of the age-related changes in Kp,vivo of cefazolin and IS was in the order of 1-week-old greater than 7-week-old = 100-week-old greater than 50-week-old rats. This is well correlated with the age-related changes in the volume of distribution at the steady state of cefazolin per body weight (Vdss/BW) and the extracellular fluid volume per body weight (Vecw/BW) determined previously using [14C]inulin. The predicted Kp value (Kp,pred) was estimated by incorporating the serum protein binding parameters of cefazolin, the IS values, and an interstitial-to-plasma albumin concentration ratio (AR) into equations derived from an extracellular fluid model. The Kp,pred values exhibited a fairly good correspondence with the Kp,vivo values determined for various organs, except gut, in rats of all four ages. These results suggest that the determinant of the age-related change in Vdss/BW is the difference in the IS value of muscle and bone, while the age-related change in serum protein binding plays only a modest role.

Adolescent↗
PubMed1989

Effects of autonomic drugs on intraluminal pressure and excretion of rat seminal vesicles in vivo.

The effects of intravenously administered autonomic drugs on the intraluminal pressure and the excretion volume of the seminal vesicles in rats were studied. Both alpha 1-adrenergic and cholinergic stimulants produced a rapid increase in pressure and fluid excretion. alpha 1-Adrenergic stimulants elicited a sharp and single increase in pressure, while cholinergic stimulants caused a sharp increase with multiple peaks.

Adrenergic alpha-Agonists↗
PubMed1989

Effects of atropine on adrenergic responsiveness and reflex vasoconstriction in humans.

To determine whether cholinergic mechanisms contribute to blood pressure regulation, we examined the effects of atropine on pressor responses to phenylephrine and vasoconstrictor responses to the cold pressor test (CPT) and lower body negative pressure (LBNP) in 16 healthy subjects. Heart rate, blood pressure and cardiac index were significantly increased, and central venous pressure (CVP) was significantly decreased after atropine (0.04mg/kg). After atropine, pressor responses to phenylephrine at doses of 20, 40 and 80 micrograms were significantly increased by 101, 112 and 93% (p less than 0.001); however, atropine attenuated pressor responses to CPT (p less than 0.001) and forearm vasoconstrictor responses to LBNP. In 6 propranolol-treated subjects, atropine also augmented pressor responses to phenylephrine but attenuated pressor responses to CPT. These results suggest that atropine augments the pressor response to an alpha-agonist, which may be partly explained by inhibition of compensatory vascular responses mediated by cholinergic mechanisms.

Adult↗
PubMed1989

Absorptive-mediated endocytosis of a dynorphin-like analgesic peptide, E-2078 into the blood-brain barrier.

The binding and internalization of a novel analog of dynorphin-like analgesic basic peptide, [125I]E-2078 (CH3-[125I] Tyr-Gly-Gly-Phe-Leu-Arg-CH3Arg-D-Leu-NHC2H5), by isolated bovine brain capillaries were investigated. High-performance liquid chromatographic analysis showed that no significant metabolism of [125I] E-2078 occurred during incubation with brain capillaries for 30 min at 37 degrees C. The binding of [125I]E-2078 to brain capillaries increased with time and the steady-state cell-to-medium concentration ratio was 58.5 +/- 2.6 microliters/mg of protein. Approximately one-fourth of the [125I]E-2078 binding was resistant to acid wash, and showed significant dependence on temperature and medium osmolarity. The acid sensitive binding of [125I]E-2078, which presumably represents surface binding, was saturable and the Scatchard plot gave a maximal binding capacity Bmax = 147 +/- 29 pmol/mg of protein, and a half-saturation constant (KD) = 4.62 +/- 0.59 microM. Pretreatment of brain capillaries with phenylarsine oxide, an endocytosis inhibitor, completely suppressed the acid resistant binding of [125I]E-2078, but did not influence the surface binding of [125I]E-2078. The acid resistant binding of [125I] E-2078 was inhibited by poly-L-lysine and protamine, but not inhibited by insulin, transferrin, dynorphin (1-8), beta-neoendorphin, naloxone or poly-L-glutamate. Moreover, in vivo brain extraction of [125I]E-2078 in rats was 368 +/- 55% higher than that of [3H] sucrose and was significantly inhibited by 1 mM of unlabeled E-2078. These results demonstrate that E-2078 is internalized by brain capillaries via absorptive-mediated endocytosis, which is a polycation-sensitive pathway.

Animals↗
PubMed1988

Differential binding of thyroxine and triiodothyronine to acidic isoforms of thyroid hormone binding globulin in human serum.

The differential availability of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to liver from the circulating thyroid hormone binding globulin (TBG)-bound pool suggests that the two thyroid hormones may bind to different TBG isoforms in human serum. In the present study, the binding of [125I]T4 and [125I]T3 to human serum proteins was investigated by using slab gel isoelectric focusing and chromatofocusing. In normal human male serum, [125I]T4 was localized to four isoforms of TBG called TBG-I, -II, -III, and -IV, with isoelectric points (pI's) of 4.30, 4.35, 4.45, and 4.55, respectively. [125I]T3 was localized to only two isoforms of TBG, TBG-III and -IV, with pI's that were identical with those for [125I]T4. In normal female serum, [125I]T4 was localized to the same four isoforms of TBG as those of normal male serum, while [125I]T3 was localized to TBG-II, -III, -IV, and -V (pI = 4.65). In pregnant female serum, [125I]T4 was localized to five isoforms, whereas [125I]T3 was localized to four. IEF was also performed with male serum loaded with various concentrations of unlabeled T3. The Ki values of T3 binding to TBG-I, -II, -III, and -IV were 5.0, 2.4, 0.86, and 0.46 nM, respectively. The TBG isoforms in normal male serum were also separated by sequential concanavalin A-Sepharose affinity chromatography and chromatofocusing (pH range of 3.5-5.0). T4 preferentially bound to the most acidic isoforms of TBG in the pI range of 3.8-4.0, whereas the less acidic fractions (pH 4.0-4.2) bound both T4 and T3. In conclusion, this study shows that T4 and T3 do not bind to a single competitive binding site on TBG. Instead, T4 is preferentially bound by the most acidic TBG isoforms owing to a 10-fold lower affinity of T3 for these proteins.

Humans↗