bluuebunny/crossref_metadata_2025 huggingface dataset:
"Summation" of the increase in heart rate from stimulation of atrial receptors
Authors: Greenwood P. V. , Kappagoda C. T.
Published: April 2011

In dogs anaesthetized with chloralose, application of stimuli which are likely to activate left atrial (L.A.) and right atrial (R.A.) receptors (complex unencapsulated endings) has been shown to result in an increase in heart rate. The present investigation was undertaken to determine whether the response elicited by the application of one stimulus (i.e., to the left atrium) could be enhanced by the application of a second stimulus (i.e., to the right atrium) in the same animal.The L.A. receptors were stimulated by distending a small balloon at the right upper pulmonary vein-L.A. junction and the R.A. receptors by "expanding" a spherical wire cage positioned at the superior vena caval (S.V.C.)-R.A. junction. Pressures in the S.V.C., R.A., L.A., and femoral artery were measured and the electrocardiogram monitored.In eight dogs stimulation of L.A. receptors resulted in an increase in heart rate (H.R.) of 18.5 beats/min (SEM 6.0; N = 23). In the same animals stimulation of R.A. receptors resulted in an increase in H.R. of 14.6 beats/min (SEM 2.0; N = 25). Application of both stimuli simultaneously resulted in an increase of 32.2 beats/min (SEM 8.0; N = 13). In four dogs propranolol hydrochloride (0.5 mg/kg) markedly diminished the response. In three dogs the response was abolished by bretylium tosylate (10 mg/kg).It is concluded that the increase in H.R. resulting from the application of these two stimuli could be "summated" and these findings support the proposition that the receptors in the two atria act as a functional entity.
Temporal characteristics of torque-triggered neuronal responses in primate precentral cortex
Authors: Wong Y. C. , Kwan H. C. , Murphy J. T.
Published: April 2011

Adult monkeys were trained to perform a restorative movement about the wrist following a torque disturbance. The movement was guided by visual information on a video display. Recordings were made from single neurons in the forelimb area of precentral cortex. Individual neurons were identified with respect to functional coupling to single forelimb joints by means of passive sensory stimulation and intracortical microstimulation. Neurons were classified as wrist (flexion–extension (F–E)) and nonwrist (F–E). Statistical analyses of activities of these two populations revealed that those belonging to the wrist (F–E) population exhibited a lower response variability than those belonging to the nonwrist (F–E) neurons. This was true with respect to both the sensory event (perturbation) and the motor event (restorative movement) at the wrist. The results thus provide additional evidence in support of the hypothesis that neuronal populations in precentral cortex which are somatotopically identified are preferentially utilized in voluntary motor tasks.
Free fatty acid turnover and oxygen consumption. Effects of noradrenaline in nonfasted and nonanesthetized cold-adapted rats
Authors: Lafrance Louise , Lagacé Georges , Routhier Danièle
Published: April 2011

The effects of a 3-h noradrenaline (NA) infusion (1.5 μg kg−1 min−1) on the O2 consumption, the respiratory quotient (RQ), the concentration of plasma free fatty acids (FFA), and the rates of appearance (Ra) and disappearance (Rd) of plasma FFA were studied in nonfasted and nonanesthetized control and cold-adapted rats. To calculate the Ra FFA and Rd FFA, [1-14C]palmitate complexed to albumin was infused as a tracer. The concentrations of glucose and lactate in blood were also determined before and during the NA infusion. The enhanced O2 consumption produced by NA in cold-adapted rats was associated with a decreased RQ. The Ra FFA and Rd FFA were more enhanced by NA in cold-adapted than in control rats whereas the plasma FFA concentration was less elevated in cold-adapted rats. The blood lactate was barely increased by the NA infusion in cold-adapted rats and was not modified in control rats. Blood glucose was increased by NA in both control and cold-adapted rats but to a greater extent in control rats during the last 90 min of NA infusion. These results suggest that the enhanced calorigenic response to NA observed in nonfasted and nonanesthetized cold-adapted rats is related, at least partly, to an enhanced lipid metabolism; the RQ is low and Ra FFA and Rd FFA are greatly increased. However, the contribution of other energetic substrates like glucose will also be investigated in further studies.
β-Adrenergic responsiveness of rats treated chronically with isoproterenol
Authors: Barney C. C. , Katovich M. J. , Fregly M. J. , Tyler P. E.
Published: April 2011

The effect of chronic administration of isoproterenol on isoproterenol-induced thirst and isoproterenol-induced changes in heart rate and selected organ weights of male rats was studied. Administration of 25 μg isoproterenol/kg, s.c., in saline daily for 10 days was accompanied by a significant attenuation of the characteristic increase in water intake following a challenging dose of isoproterenol (25 μg/kg, s.c.) on the 11th day. Administration of 25 μg isoproterenol/kg, s.c., every 2nd, 3rd, or 4th day for 10 days was without significant effect on water intake following isoproterenol (25 μg/kg, s.c.) on the 11th day. Administration of 25 μg isoproterenol/kg, s.c., every day for 10 days led to a slight increase in cardiac responsiveness to a challenging dose of isoproterenol (25 μg/kg) on the 11th day. Chronic treatment with this low dose of isoproterenol for 10 days was also accompanied by a significant increase in the ratio of heart weight to body weight but no significant changes in the ratio of kidney, adrenal, thyroid, spleen, or interscapular brown fat to body weight. Thus, daily administration of the β-adrenergic agonist isoproterenol for 10 days can alter β-adrenergic responsiveness in the rat with β1 (heart rate) and β2 (thirst) mediated responses showing opposite effects. In addition, the results suggest that tests of β-adrenergic responsiveness must be assessed in terms of the frequency of administration of the agonist.
Smooth muscle membrane vesicle orientation: a study on intactness and sidedness of rat myometrium plasma membrane vesicles
Authors: Grover A. K. , Crankshaw J. , Garfield R. E. , Daniel E. E.
Published: April 2011

Plasma membrane vesicles of rat myometrium were prepared in media containing 240 mM sucrose. The vesicles were exposed to isotonic, hypertonic, and hypotonic sucrose concentrations, fixed, sectioned, and studied using the electron microscope. The vesicles fixed in isotonic media were circular in appearance. Vesicles fixed in hypertonic media were distorted and showed a reduced volume to surface ratio consistent with the hypothesis that >80% of the vesicles were osmotically active to sucrose. Cationized ferritin binding studies and Ca binding and release studies were also consistent with this finding. Exposure to hypotonic media also yielded membranes with distorted profiles indicating that they had been ruptured. [3H]Sucrose trapping experiments revealed that the vesicles had an internal volume of 1.20–1.44 mL/g protein. Hypotonic shock treatment reduced this intravesicular volume to 0.20–0.28 mL/g protein. The hypotonic shock treatment also led to enhanced galactose oxidase catalyzed Na3B3H4 labelling of the membranes and to increased K+-activated ouabain-sensitive p-nitrophenyl phosphatase activity. The enhancement was the same (55 ± 10%) in the various membrane preparations for both the parameters. The data are interpreted to conclude that the rat myometrium plasma membrane vesicles consisted of 20% broken vesicles and equal proportions of intact vesicles of inside-out and rightside-out orientations.
The effect of α-bungarotoxin on spontaneous activity in the ventral nerve cord of Limulus polyphemus
Authors: Thomas William , Townsel James G.
Published: April 2011

The physiological action of α bungarotoxin in the central nervous system of the horseshoe crab Limulus polyphemus was investigated. Two types of effects were produced by the toxin. The predominant effect was an inhibition of spontaneous activity. However, in some instances α bungarotoxin caused a stimulation of activity. In both cases the action of the toxin resembled the effect of d-tubocurarine and opposed the effect of carbamylcholine. Both effects of α-bungarotoxin were maximal within 15 min and were sustained for at least 2 h. These results suggest that α-bungarotoxin acts as a cholinergic antagonist in the central nervous system of Limulus and are consistent with the specific binding of the toxin to an acetylcholine receptor.
Relationship of plasma motilin concentration to fat ingestion, duodenal acidification and alkalinization, and migrating motor complexes in dogs
Authors: Fox J. E. T. , Track N. S. , Daniel E. E.
Published: April 2011

Plasma motilin concentrations were measured in dogs following duodenal acidification and alkalinization and gastric instillation of fat. Antral and duodenal motility were recorded concurrently using intraluminal manometry. Alkalinization of the duodenum produced an increase in antral and duodenal motility and a significant rise in plasma motilin. Alkaline infusions at 5 mL/min into the duodenum initiated phase III of a migrating motor complex both in the antrum and in the duodenum. Duodenal acid infusions produced no change in plasma motilin concentrations while inhibiting antral motility and stimulating duodenal motility for the duration of the infusion. Gastric instillation of 60 g fat produced a 25% increase above basal motilin levels at 50 min after instillation. Motilin levels monitored during spontaneous migrating motor complexes showed peak motilin levels occurring during maximal activity of the antral duodenal region in seven out of nine motor complexes examined but motilin peaks also occurred without migrating complexes being present in this area and, as well, complexes occurred when motilin was undetectable. These results taken together with our other studies in man confirm that a true species difference exists between man and dog in the hormonal motor response to duodenal alkalinization. Although a relationship appears to exist between the appearance of maximal migrating motor complex activity in the gastroduodenal area and plasma motilin concentrations in dogs as in humans, the motilin peaks are probably neither necessary nor sufficient to induce phase III activity.
Axonal transport in dystrophic hamsters
Authors: Boegman R. J. , Wood P. L.
Published: April 2011

Axonal transport of [3H]proline, [3H]fucose, and choline acetyltransferase (CAT) was examined in 20-, 50-, and 100-day-old dystrophic and control hamsters. Irrespective of the age of the animal and therefore of the degree of muscle necrosis, there were no significant differences in the velocity of axonal transport of labelled protein or glycoprotein or in the accumulation of CAT at a nerve ligature between dystrophic and normal hamsters.
Structure–activity study of kinins in vascular smooth muscles
Authors: Gaudreau P. , Barabé J. , St-Pierre S. , Regoli D.
Published: April 2011

To explore further the relations between the chemical structure and the biological activities of kinins, a series of bradykinin fragments and analogues was prepared by the solid-phase method. Bradykinin and kallidin were also extended at the C- or the N-terminai end by the addition of one or more residues in order to evaluate the importance of peptide chain length and of additional positive charges at the N-terminal end for the biological activity. After purification by cation-exchange chromatography and gel filtration, the compounds were characterized by thin-layer chromatography, paper electrophoresis, elemental analyses, and amino acid analyses. All compounds were tested on three vascular preparations (the dog common carotid artery, the rabbit jugular vein, and the guinea pig anterior mesenteric vein) in order to measure their relative potencies as relaxant (on the dog common carotid artery) or as stimulant (the two veins) of vascular smooth muscles. The compounds were also tested on the cat terminal ileum and the rabbit aorta for comparison.The results reported in this paper indicate that all the new analogues of bradykinin as well as some fragments and analogues described before by us and by other workers are full agonists in the three vascular preparations. No partial agonists or antagonists have been identified. The order of potency of the various kinin analogues is similar in the three vascular preparations and follows the same pattern as that found in the cat terminal ileum. It is therefore concluded that (a) the three vascular preparations utilized in the present experiment possess a B2 receptor type that appears to be similar to that of the cat terminal ileum and of the rat uterus described before and (b) receptors of the B2 type are able to mediate both the inhibitory and the excitatory actions of kinins in vascular smooth muscles.
Saturable binding of [3H]phenytoin to rat brain membrane fraction
Authors: Burnham W. M. , Spero L. , Okazaki M. M. , Madras B. K.
Published: April 2011

Preliminary studies indicate that [3H]phenytoin binds in a saturable and reversible fashion to at least two distinct sites in the membrane fraction of whole rat brain. One of these displays a high affinity (Kd = 6 nM) and a low maximal capacity (Bmax = 10 pmol/g protein). The other has a low affinity (Kd = 4.8 μM) and is estimated to have a very high maximal capacity. Phenytoin binding is reduced if the membrane fraction is preincubated with proteolytic enzymes and subcellular fractionation studies indicate that the P2 fraction has the largest number of binding sites. Competition experiments fail to reveal significant binding interactions with putative neurotransmitters or with other drugs except the hydantoins and anticonvulsant barbiturates. Although it is premature to speculate on the clinical significance of these findings, it is encouraging to note that the low affinity site has a Kd very similar to the therapeutic levels of phenytoin found in cerebrospinal fluid and that there seems to be some relationship between binding potency and anticonvulsant potency within the hydantoin series.
Alteration of acetylcholine receptor and acetylcholinesterase metabolism by actinomycin D In cultured muscle cells
Authors: Weidoff Jr. Paul M. , McNamee Mark G. , Wilson Barry W.
Published: April 2011

Actinomycin D (ACT-D), an inhibitor of transcription, was added to chick muscle cultures to study its effect on the synthesis of acetylcholine receptor (ACHR) and acetylcholinesterase (ACHE, EC 3.1.1.7). Doses of ACT-D (1.85–18.5 nM), which inhibited uridine incorporation up to 80%, increased ACHR, ACHE, and creatine kinase (CK, EC 2.7.3.2) levels without affecting general cell protein. Degradation of ACHR was slower in ACT-D treated cultures than controls, resulting in a twofold increase in receptor half-life. Uridine incorporation was inhibited by ACT-D in both mononucleated cells and myotubes and [3H]uridine nuclear grain distributions were shifted to values lower than controls. The results indicate that posttranscriptional effects of ACT-D increase levels of ACHR, ACHE, and CK and that decreased degradation could account for the increase in the number of surface ACH receptors.
The effects of androgens and estrogens on human prostatic cells in culture
Authors: Hudson Robert W.
Published: April 2011

A ceil culture system has been developed in order to assess the response of human prostatic carcinoma cells to the presence of androgens and estrogens. A single cell suspension of these cells was incubated in minimum essential medium, in the absence of added sex steroids (standard culture), for 24 h. Equal aliquots of these cultured cells were incubated for a further 24–72 h in standard medium or in medium to which testosterone (T, 17.4 nM), dihydrotestosterone (DHT, 1.7 nM) or estradiol (E2, 0.36 nM) had been added. At the end of the incubations, the levels of tartrate-inhibitable acid phosphatase were compared in the standard cultures and the cultures to which sex steroids had been added.There were three patterns of response of patients' cells to the presence of androgens. From a total of 91 cell cultures, obtained from 85 patients, androgens were associated with an increased acid phosphatase production in 58. In 22 incubations, there was no androgenic effect on acid phosphatase production, and in II incubations, androgens were associated with lower enzyme levels than in the standard cultures. The qualitative effects of T and DHT were the same, but the quantitative effect of DHT was greater than that of T in those experiments in which there was a positive androgenic effect on acid phosphatase production. In 10 of 46 incubations with E2, acid phosphatase levels were lower than the standard incubations, while in 28 there was no difference in enzyme levels. In eight incubations, E2 was associated with a greater acid phosphatase production than that found in the standard cultures.In cultures of the cells from 180 men with benign prostatic hyperplasia and 5 men with normal prostatic tissue, androgens and estrogens had no effect on acid production by these cells, even at DHT concentrations of 1.7 × 10−7 M.It is concluded that prostatic carcinoma cells behave differently, in culture, in response to sex steroids, than do cells from benign hyperplastic or normal prostatic tissue.
Effects of low concentrations of ethanol on CA1 hippocampal neurons in vitro
Authors: Durand D. , Corrigall W. A. , Kujtan P. , Carlen P. L.
Published: April 2011

The effects of ethanol (10, 20, 50, and 100 mM) have been studied on field potentials in the CA1 region of the in vitro hippocampal slice preparation. Ethanol produced depression of the orthodromically evoked CA1 population spike and raised the threshold for orthodromic spike production. The effects of ethanol on the size of the population spike were highly correlated with the amount of the inhibition present in the slice as measured by paired pulse stimulation in control medium. Ethanol increased recurrent inhibition in the slice but had no significant effect on the antidromic response and produced only small changes in the dendritic field potential amplitudes. Adaptation or acute tolerance to the depressing effects of ethanol was observed in many slices. It is suggested that ethanol acts by potentiating the intrinsic inhibitory system in the hippocampus.
Dual influence of hydralazine on constrictor response to noradrenaline in isolated arterial smooth muscle
Authors: Krishnamurty V. S. R.
Published: April 2011

The effects of hydralazine (Hyd) on vascular smooth muscle contractile response to α-receptor stimulation by exogenous and endogenous noradrenaline (NA) in the absence and presence of Mg2+ (1.2 mM)were examined using a proximal segment of rabbit's ear artery. Intraluminal perfusion with Hyd (2 × 10−4 M) in normal Krebs bicarbonate medium inhibited the NA-induced contraction only in the presence of Mg2+ (1.2 mM) in the medium. The extraluminal superfusion of the artery with Hyd (2 × 10−4 M) enhanced the vasoconstriction to extraluminally superfused NA in either the presence or absence of Mg2+ in the medium. However, when the artery was preincubated with an adrenergic neuron blocker, guanethidine (3.2 × 10−6 M), Hyd (2 × 10−4 M) inhibited NA-induced vasoconstriction. Contrary to the effects of Hyd on intraluminal NA, Hyd potentiated the response of this superfused artery to electrical stimulation in the presence of Mg2+ (1.2 mM) whereas in the Mg2+-free medium, it inhibited the constriction. These findings suggest that Hyd may have dual effects on isolated vascular smooth muscle by directly inhibiting the contractile activation and indirectly by an interference at adrenergic nerves, which potentiates the effects of exogenous NA and(or) alters the release of endogenous NA.
On the suitability of Innovar, a neuroleptic analgesic, for cardiovascular experiments
Authors: Brill Richard W. , Jones David R.
Published: April 2011

The effects of 0.2 and 0.5 mL/kg Innovar (a neuroleptic analgesic) on cardiovascular functions and reflexes in rabbits were measured. We recorded the effects of Innovar on arterial pressure, heart rate, respiration rate, ventricular contractility, and arterial oxygen tension, as well as the drug's effects on the bradycardia and vasoconstrictor response to cigarette smoke stimulation of the nose (the so-called "nasopharyngeal reflex").In animals given 0.2 mL/kg Innovar, all steady state cardiovascular variables had returned to pre-Innovar levels in 45 min, as had the efficacy of the nasopharyngeal reflex. In animals given 0.5 mL/kg Innovar, all steady state cardiovascular variables, except [Formula: see text] were slightly but significantly depressed for up to 135 min after injection. The nasopharyngeal reflex returned to normal within 90 min.Because of the calmative and analgesic effects of Innovar, and its only moderate effects on cardiovascular functions and reflexes, we feel it is a suitable neuroleptic analgesic agent for cardiovascular experiments where neither fully conscious nor surgically anesthetized animals can be used.
Calcium activation of sarcoplasmic reticulum ATPase following strenuous activity
Authors: Belcastro A. N. , Rossiter M. , Low M. P. , Sopper M. M.
Published: April 2011

The purpose of this study was to examine the effects of varying Ca2+ concentration on the Ca2+ activated sarcoplasmic reticulum (SR) ATPase activity of fast-twitch (FT) skeletal muscle at exhaustion and during recovery. Wistar rats (200 g) were assigned to control (C), exhausted (E), and three recovery groups (R) at 5, 15, and 30 min. Following exhaustion on a motor-driven treadmill, the gastrocnemius muscles from all groups were excised and frozen. Muscle samples were assayed for ATPase activity in a Ca2+ – ethyleneglycol bis (β-aminoethyl ether)-N,N′-tetraacetic acid (EGTA) buffering system. At 1.25 μM Ca2+, a significant depression in Ca2+ activated ATPase activity occurred in the E, 5R, 15R, and 30R groups (1.61 ± 0.17, 1.87 ± 0.14, 1.43 ± 0.29, and 1.62 ± 0.1 μmol Pi∙mg−1∙10 min−1) compared with C values (2.41 ± 0.34 μmol Pi∙mg−1∙10 min−1) (p ≤ 0.05). At 5.0 μM, Ca2+ activated ATPase activity remained depressed in the E, 5R, and 15R groups compared with C and 30R groups (p ≤ 0.05). At 0.75 μM Ca2+, there was no significant difference between groups (p ≥ 0.05). The results suggest that Ca2+ activated SR ATPase activity of fatigued FT muscle may contribute to the decreased force production at exhaustion.
Isolation and characterization of subcellular membranes from canine stomach smooth muscle
Authors: Sakai Y. , McLean J. , Grover A. K. , Garfield R. E. , Fox J. E. T. , Daniel E. E.
Published: April 2011

Subcellular membrane fractions were isolated from the circular muscle of the corpus of canine stomach by differential and isopycnic sucrose density gradient centrifugation. Differential centrifugation gave a mitochondrial fraction enriched (fourfold) in cytochrome c oxidase and a microsomal fraction enriched (fourfold) in 5′-nucleotidase and NADPH–cytochrome c reductase over postnuclear supernatant. On the basis of a study using continuous gradient, a discontinuous sucrose density gradient was prepared to yield F1 to F5 fractions. The F3 fraction at the interface of 18–32% (w/w) sucrose was maximally enriched (13-fold) in 5′-nucleotidase. The fraction contained very low levels of cytochrome c oxidase but did contain NADPH–cytochrome c reductase (eightfold enrichment). The F4 fraction, at the interface of 32–40% (w/w) sucrose, was maximally enriched in NADPH–cytochrome c reductase (12-fold) and cytochrome c oxidase (6-fold). The distribution of the azide-insensitive, ATP-dependent Ca2+ uptake correlated very well with that of 5′-nucleotidase but less well with NADPH–cytochrome c reductase and not at all with cytochrome c oxidase. Sodium azide and ruthenium red inhibited the ATP-dependent Ca2+ uptake by the mitochondrial fraction and postnuclear supernatant, but not by the F3 fraction. ATP-dependent Ca2+ uptake by the F3 fraction was inhibited by calcium ionophores A23187 and ionomycin, but not by the sodium ionophore, monensin. These results are consistent with the hypothesis that the plasma membrane plays a major role in regulating intracellular Ca2+ concentration in canine corpus circular muscle.
Phospholipase A2 stimulated release of prostanoids from the isolated, perfused rabbit liver: implications in regional cellular injury
Authors: Flynn John T. , Henry Joseph M. , Perkowski Sandra
Published: April 2011

We have previously demonstrated a direct relationship between the activity of the arachidonic acid cascade in vivo and the extent of cellular damage following several types of experimental injury. Since phospholipase activity has been shown to regulate arachidonic acid availability, we tested the ability of circulating phospholipase A2 (PLA2) of pancreatic origin to stimulate prostanoid production or induce cellular injury in the isolated, perfused rabbit liver. Experimental conditions were similar to those present during pancreatitis or early splanchnic artery occlusion shock. The administration of PLA2 at a rate of 100 U/min for 10 min resulted in enhanced rates of thromboxane B2 and 6-ketoprostaglandin F1α release between 1 and 5 min into the infusion period. No changes in hepatic perfusion pressure, vascular resistance, wet tissue weight, or release of lactic dehydrogenase or acid phosphatase into the effluent were observed in either vehicle or PLA2-treated livers. This indicates that cellular injury was not a factor in the prostanoid release. These data suggest that circulating PLA2 can directly stimulate de novo prostanoid synthesis in noninjured tissues. Thus, enhanced plasma prostanoid concentrations in intact animals during periods of regional cellular injury may be due in part to circulating PLA2 released from damaged tissues.
Ba2+ ions block K+-induced contractures by antagonizing K+-induced membrane depolarization in frog skeletal muscle fibres
Authors: Frank George B. , Rohani Farrokh
Published: April 2011

The effects of Ba2+ ions on twitches. K+-induced contractures, and on intracellularly recorded membrane potentials (Em) and depolarizations of frog skeletal muscle fibres were investigated. Exposure of toe muscles to choline–Ringer's solution with 10−3 M Ba2+ with Ca2+ (1.08 mM) eliminated or very greatly reduced contractures produced by 60 mM K+. In contrast, not only did the same concentration of Ba2+ ions fail to depress the twitch tension of isolated semitendinosus fibres when added to Ringer's with Ca2+, but it even restored twitches that had been eliminated in a zero Ca2+ Ringer's solution. The resting Em of sartorius muscle fibres in choline–Ringer's solution was reduced about 20 mV by 10−3 M Ba2+. This Ba2+ ion concentration also antagonized the K+-induced depolarization. Thus in the presence of 1 mM Ba2+, 20 mM K+ hyperpolarized rather than depolarized the fibres and 60 or 123 mM K+ produced only very slowly developing, small depolarizations. These results suggest that the loss of the K+-induced contracture in choline–Ringer's caused by Ba2+ ions is due to an inhibition of the K+-induced depolarization. The latter result is consistent with previous findings of other workers that Ba2+ ions block membrane K+ channels.not available
Use of 3-O-methyI-D-glucose and phloretin to estimate the intracellular water space of mouse peritoneal macrophage monolayers
Authors: Lowrie Douglas B.
Published: April 2011

Macrophages took up 3-O-methyl-D-glucose rapidly by facilitated diffusion using the glucose carrier and slowly by carrier-independent diffusion. Phloretin inhibited carrier-dependent but not carrier-independent diffusion. Estimates of intracellular water space based on 3-O-methyl-D-glucose uptake varied between 0.7 and 6.9 μL∙106 cells−1 for 2-week-old monolayers.
Influence of diets on the effect of probenecid and of cold exposure under restraint on noradrenaline and serotonin in the hypothalamus
Authors: Héroux Olivier
Published: April 2011

Male Sprague–Dawley rats (300 g) fed a laboratory chow (P-diet) have been shown previously to be less resistant to cold than similar rats fed a semipurified diet (H-diet). In a subsequent study, determinations of a series of parameters related to the metabolism of serotonin (5-HT) revealed a more active central serotoninergic system in P-diet fed rats.In the present study, an attempt was made at measuring the turnover rate of 5-HT in hypothalamus of both P- and H-diet fed rats, using the probenecid test. Secondly, the influence of the two diets on the metabolism of 5-HT and noradrenaline (NA) in hypothalamus during cold exposure under restraint was examined by determining the hypothalamic contents of 5-HT, 5-hydroxyindolacctic acid (5-HIAA), and NA at different times during cold exposure. The administration of probenecid (200 mg/kg i.p.) at 28 °C resulted in an accumulation with time of 5-HT and 5-HIAA and a decrease of NA in hypothalamus of P-diet fed rats but not in H-diet fed rats. In the cold, probenecid reduced the accumulation of 5-HT and 5-HIAA observed in the P-diet controls, but did not influence their NA loss; in H-diet fed rats it had no effect at all on their 5-HT, 5-HIAA, and NA hypothalamic contents. On both diet groups, however, probenecid severely curtailed thermoregulation. Because the probenecid effect on the 5-HIAA transport was diet dependent, because this effect was not specific (NA being affected), and because it had some unknown damaging consequences resulting in a complete failure to thermoregulate in the cold, probenecid was considered as completely inadequate for measuring the 5-HT turnover rate. Cold exposure under restraint resulted in severe hypothermia and in an accumulation of 5-HT, 5-HIAA, and a loss of NA in hypothalamus of control P-diet fed rats; the initial hypothalamic content remained unchanged in H-diet fed rats, which showed a great degree of stress resistance. It is suggested that stress tolerance may depend on the capacity to maintain the initial equilibrium between 5-HT and NA contents in hypothalamus, capacity which apparently is diet dependent.
Intracellular calcium translocation during contraction in vertebrate and invertebrate smooth muscles as studied by the pyroantimonate method
Authors: Sugi Haruo , Suzuki Suechika , Daimon Tateo
Published: April 2011

The intracellular localization of activator Ca and its translocation during the mechanical activity were studied on vertebrate and invertebrate smooth muscles by fixing muscle fibers with a 1% OsO4 solution containing 2% potassium pyroantimonate for electron microscopic examination. When guinea-pig tacnia coli, Mytilus anterior byssal retractor muscle, and Dorabella longitudinal body wall muscle were fixed during the relaxed state, electron-opaque pyroantimonate precipitate containing Ca was localized along the inner surface of the plasma membrane and at other membranous structures in close apposition to the plasma membrane, in accordance with physiological evidence that these muscles contain intracellularly stored activator Ca. When they were fixed during the contracted state, the precipitate was distributed diffusely in the myoplasm in the form of small particles, indicating the release of activator Ca from the peripheral structures. The contraction in dog coronary artery smooth muscle appears to be associated with the inward movement of extracellular Ca. In accordance with this, the resting coronary artery muscle fibers exhibited the precipitate in the lumen of the caveolae, i.e., the bottle-shaped plasma membrane invaginations, but not at the peripheral intracellular structures, though the contracted fibers showed the diffuse distribution of the precipitate in the myoplasm. These results indicate that the pyroantimonate method is very effective in studying the translocation of activator Ca in various types of smooth muscle.
Depression of uterine blood flow in response to cord compression in sheep
Authors: Cottle M. K. W. , Petten G. R. Van , Muyden P. van
Published: April 2011

Seven conscious chronically cannulated ewes and their fetuses were studied in the third trimester of pregnancy. Compression of the umbilical cord for 4 min, to a degree simulating the occurrence in clinical obstetrics, not only produced the expected fetal hypoxia, acidemia, and cardiovascular effects but also significantly reduced uterine blood flow. In a ewe with twin fetuses, compression of the cord to only one fetus decreased the flow to that horn and had no effect on flow to the other horn. It is postulated that the reduction in uteroplacental flow was due to stimulation of α-adrenoceptors in the maternal placental vasculature by catecholamines of fetal origin, or the effects of increased tissue-fluid pressure in the fetal placenta, or a combination of these mechanisms.
Estradiol-17β and androgen secretion by isolated porcine ovarian follicular cells in vitro
Authors: Tsang B. K. , Moon Y. S. , Armstrong D. T.
Published: April 2011

The cellular sources and gonadotropic regulation of porcine ovarian estrogen and androgen were assessed by culturing isolated granulosa cells and thecal cells from medium size follicles (4–6 mm diameter) separately for 24 h in a chemically defined medium containing gonadotropins and (or) testosterone. At the end of the culture period, estradiol-17β (estradiol) and androgens in the media were determined by radioimmunoassays. Production of estradiol by granulosa cells without an exogenous aromatizable androgen was low in the absence or presence of a highly purified preparation of either follicle-stimulating hormone (FSH, 0.25 μg/mL) or luteinizing hormone (LH, 1 μg/mL). Addition of testosterone or androstenedione (0.5 μM), but not dihydrotestosterone or pregnenolone, significantly increased estradiol secretion. Additional increases were observed when FSH, LH, prostaglandin E2, or dibutyryl cyclic 3′,5′-adenosine monophosphate was present. Production of estradiol by thecal cells was low in the presence or absence of exogenous testosterone, and was essentially unaffected by the presence of gonadotropins. Thecal cells, however, released large amounts of androstenedione and smaller amounts of testosterone and other androgens during 24-h culture and the production of these androgens was stimulated by LH but not by FSH. Androgen secretion by granulosa cells was negligible when compared with the theca and was unaffected by gonadotropins. It is concluded that the theca is the prime site for follicular androgen biosynthesis by the porcine ovarian follicle, and, upon LH stimulation, may provide androgen precursors for estradiol production by granulosa cells.
Cerebrospinal fluid formation in rats and cats during treatment with timolol
Authors: Vogh Betty P. , Godman David R.
Published: April 2011

The influence of timolol upon cerebrospinal fluid formation rate has been examined in rats by the measurement of 22Na+ entry into this fluid after 10, 100, or 1000 μg∙kg−1 i.v, and in cats by the dye-dilution measurement of new fluid formation after 30, or 3000 μg∙kg−1 i.v., or 250 μg∙mL−1 in ventricular perfusate. In rats no change from control rates occurred. In the cats there appeared to be no effect of intraventricular timolol; however, a significant decrease of ~ 25% in the mean flow rate was seen after 40 min when drug was given i.v. at either dose level. A time study showed that no further decrease occurred within 5 h and that the observed decrease continued for at least 3 h. These findings are of interest in view of the ability of topical, intraocular, and i.v. timolol to reduce aqueous humor formation rate.
Plasma catecholamines and response to exercise in 6-hydroxydopamine-treated dogs
Authors: Péronnet François , Nadeau Réginald , Champlain Jacques de , Imbach Andrée
Published: April 2011

Plasma catecholamine (CA; picograms per millilitre) concentrations were measured simultaneously with heart rate (HR, beats per minute) during short-duration exercise, and with plasma glucose, lactate, and free fatty acid (FFA) concentrations (millimoles per litre) during long-duration exercise, in control dogs (N-dogs) and in sympathectomized dogs (S-dogs) with 6-hydroxydopamine (50 mg∙kg−1). At rest, higher plasma CA in S-dogs (690 ± 90 vs. 320 ± 60) was associated with higher HR (126 ± 3 vs. 90 ± 5), plasma glucose (6.4 ± 0.2 vs. 5.1 ± 0.2), lactate (2.9 ± 0.2 vs. 1.6 ± 0.2), and FFA concentrations (1.08 ± 0.11 vs. 0.81 ± 0.11). During short-duration exercise a normal HR response in S-dogs (226 ± 9 vs. 228 ± 8) was dependent upon larger than normal plasma CA values (4280 ± 680 vs. 1990 ± 360). Metabolic adjustments to long-duration exercise were impaired in S-dogs as evidenced by the higher plasma glucose and lactate concentrations (8.2 ± 0.5 and 5.5 ± 0.3 vs. 6.4 ± 0.4 and 4.6 ± 0.3) and the lower plasma FFA concentration (0.66 ± 0.16 vs. 1.20 ± 0.09). These occurred despite a normal plasma CA response in S-dogs (6850 ± 1450 vs. 8740 ± 1680). Following chemical sympathectomy the adrenal medulla can compensate to ensure an adequate heart rate response to short-duration exercise, but not to ensure adequate metabolic adjustments to prolonged exercise.
Ouabaïne et activité intracellulaire du K dans le muscle papillaire du lapin
Authors: Désilets Michel , Caillé Jean-Pierre
Published: April 2011

Ionic activity on both sides of the cardiac cell membrane is an essential parameter for determining the mechanism responsible for the positive inotropic effect of cardiotonic glucosides. The intracellular activity of [Formula: see text] was therefore measured using selective microelectrodes, in the papillary muscles of a rabbit, for both a low concentration (10−8 M) and a toxic concentration (10−6 M) of ouabain.The ouabain at low concentration (10−8 M) had no significant effect with respect to [Formula: see text], the values derived with and without ouabain being 85.4 mequiv./L and 84.2 mequiv./L respectively. The use of selective microelectrodes for measuring K, paired with a microelectrode filled with KCl, made it possible to study [Formula: see text] in terms of time in the presence of a toxic concentration of ouabain (10−6 M). In such a case, ouabain results in a reversible lessening of [Formula: see text].[Journal translation]
Effect of naloxone on ethanol- and pentobarbital-induced narcosis
Authors: Khanna J. M. , Mayer J. M. , Kalant H. , Shah G.
Published: April 2011

Single or repeated subcutaneous administrations of naloxone in doses of up to 4 mg∙kg−1 did not alter the time for onset or the duration of ethanol- or pentobarbital-induced narcosis in rats. An increase in the naloxone dosage to 50 mg∙kg−1 s.c. resulted in a small reduction of ethanol-induced sleep duration. Repeated i.p. or i.v. administrations of much higher doses of naloxone (300–400 mg∙kg−1 and 120–180 mg∙kg−1, respectively) did produce significant reductions in ethanol-induced narcosis. However, similar naloxone doses, when administered alone, i.v., had marked convulsant effect. It appears that naloxone, in low doses, is not an effective antidote for narcosis caused by ethanol or pentobarbital at the ethanol and pentobarbital doses tested, whereas the antagonism of ethanol-induced sleep by high doses of naloxone may be due to the analeptic action of this drug.
Introduction: free radical involvement in physiological and biochemical processes
Authors: Petkau A.
Published: April 2011

Specific physiological and biochemical processes are referenced to illustrate the multifarious involvement of free radicals and other forms of activated oxygen in living systems. This involvement may have a subtle origin and lead to greatly amplified effects.
On the safety of treatment with bovine superoxide dismutase: production of a humoral antibody response in rabbits with repeated treatment
Authors: Kelly K. , Boux H. , Petkau A. , Sehon A.
Published: April 2011

Treatment of rabbits with sterile solutions of bovine Cu-Zn superoxide dismutase according to schedules recommended for radiation cystitis and radiation side effects has elicited the production of antibodies to the enzyme, detected in rabbit sera by a sensitive and specific radioimmunoassay. No antibodies were detected after a single treatment. However, on repeated administration of the enzyme all animals, including those that received 4 Gy whole body radiation prior to treatment, produced detectable antibody. Titers of antibody in sera rose progressively with repeated injections of the enzyme. Irradiation served merely to delay the onset of the immune response. In addition, human and bovine Cu-Zn superoxide dismutase have been found to be antigenically distinct when examined by competitive inhibition radioimmunoassay. These antigenic differences and the immunogenicity of the bovine enzyme in rabbits raise reasonable doubt as to the safety of administration of bovine superoxide dismutase to human patients. It is recommended that such patients be monitored for antibody production, preferably by radioimmunoassay.
The occurrence of two hepatic microsomal sites for amobarbital hydroxylation
Authors: Reilly P. A. , Tang B. K. , Stewart D. J. , Kalow W.
Published: April 2011

Amobarbital metabolism in human liver and in rat liver, lung, kidney, and small intestine was measured in vitro using thin-layer chromatography (TLC) for separation of metabolites generated from incubation with [2-14C]amobarbital. Formation of 3′-hydroxyamobarbital (C-OH) occurred primarily in the liver. The kinetics of C-OH formation by rat liver microsomes or isolated hepatocytes could be described by a Michaelis–Menten model incorporating two metabolic sites, one characterized by high-affinity and low-velocity constants (Km = 0.054 ± 0.012 mM, Vmax = 16.89 ± 4.27 nmol C-OH∙g liver−1∙min−1), the other by low-affinity and high-velocity (Km = 0.679 ± 0.097 mM, Vmax = 66.0 ± 5.41 nmol C-OH∙g liver−1∙min−1). The kinetic parameters of the high-affinity site differed significantly between whole cells and homogenates. Pretreatment with phenobarbital for 3 days induced only the high-affinity site. Quantitation of C-OH formation in four human liver samples from several sources showed that metabolism may conform to the two-site model observed in rat liver.
Diurnal variation in urine [15N]urea content, estimates of whole body protein turnover, and isotope recycling in healthy meal-fed children with cystic fibrosis
Authors: Parsons H. G. , Wood M. M. , Pencharz P. B.
Published: April 2011

The pattern of urinary urea excretion and labelling with 15N was examined in eight meal-fed 6 to 9 year old children, over a 3-day period using a simulated constant infusion of the label. The children had cystic fibrosis but were healthy and in a good nutritional status at the time of the study. Reciprocal diurnal patterns of urea excretion and [15N]urea enrichment were noted and found to be suitable for mathematical description. Urea excretion was maximal in the evening at approximately 2000 and minimal at 0800, whereas the [15N]urea enrichment was maximal at about 0800 and minimal at 2000. In addition to the diurnal variation the [15N]urea enrichment increased exponentially to a plateau or isotopic steady state. The diurnal variation in [15N]urea enrichment resulted in large diurnal changes in the calculated rates of whole body amino nitrogen flux, synthesis, and breakdown. Flux rates were approximately 44% higher in the evening than in the morning. Synthesis rates were 19% higher in the evening, whereas breakdown rates were 27% greater in the morning. Mean amino nitrogen flux rates were 1.28 (SD 0.13) g N∙kg−1∙day−1. Isotope recycling was estimated from the slope of the [15N]urea enrichment curve between 30 and 54 h from the start of the study. There was a wide range in recycling, 2.9–19.4% (mean 11.4, SD 5.4). Some of the biological and pharmacological importance of the diurnal variation in the protein metabolism is discussed.
Effect of aging on response to induction and metabolizing activity of the hepatic mixed-function oxidase system of male Sprague–Dawley rats
Authors: Sitar Daniel S. , Desai Chetan D.
Published: April 2011

The composition and activity of the rat hepatic mixed-function oxidase system were investigated, in male rats 17 to 127 weeks old, with respect to content of its various components and their response to induction by phenobarbital and β-naphthoflavone. There were decreases in many of the components of this enzyme system in older rats which could not be fully compensated by phenobarbital induction. However, there appeared to be no age-related loss of response to induction by β-naphthoflavone. Decreases in mixed-function oxidase enzymes with age did not occur at the same rate or to the same extent. Metabolic studies with ethylmorphine and aniline demonstrated some age-associated changes which did not necessarily parallel reductions in the enzyme system. For example, there was a reduction in apparent Km as a function of age for the hydroxylation of aniline in rats treated with β-naphthoflavone, even though they showed no apparent change in the amount of cytochrome P-450. There was also a trend to altered Km for the demethylation of ethylmorphine in saline or corn oil treated rats in older animals. We feel that these changes are a reflection of differential reductions in the various isozymes of cytochromes P-450. Further studies are planned to confirm this hypothesis.
Inhibition of uroporphyrinogen decarboxylase by 3,3′,4,4′-tetrachlorobiphenyl in chick embryo liver cell culture
Authors: Swain M. G. , Follows S. B. , Marks G. S.
Published: April 2011

An assay was developed to measure uroporphyrinogen decarboxylase activity in 17-day-old chick embryo liver cells in culture. Decarboxylation products arising from the action of uroporphyrinogen decarboxylase upon uroporphyrinogen III were quantitated using high-pressure liquid chromatography. 3,3′,4,4′-Tetrachlorobiphenyl (TCBP) was added to chick embryo liver cells and 24 h later the uroporphyrinogen decarboxylase activity in the ceils was measured; a significant inhibition was found. On the other hand, when TCBP was added directly to the crude uroporphyrinogen decarboxylase enzyme no inhibition was noted. The inhibition of uroporphyrinogen decarboxylase observed in this study explains the accumulation of uroporphyrin and heptacarboxylic porphyrin in chick embryo liver cell cultures treated with TCBP.
Tissue catecholamines in obstructive nephropathy and acute uremia in the rat
Authors: Wilson D. R. , Honrath U. , Sole M. J.
Published: April 2011

Previous studies have shown that the 24-h unilateral ureteral obstructed kidney (UUO) responds to acute renal denervation after relief of obstruction with an increase in glomerular filtration rate (GFR), renal plasma flow (RPF), natriuresis, and diuresis, while the 24-h bilateral ureteral obstructed kidney (BUO), undergoing postobstructive diuresis after relief of obstruction, shows no response to acute denervation. In the present study, renal tissue norepinephrine (NE) content and concentration were found to be markedly decreased in the BUO kidney suggesting partial renal denervation, while renal NE content was normal in the UUO kidney. The decrease in renal NE content in the BUO kidney was organ specific since myocardial NE was not affected, and was not due to acute uremia, since rats made uremic by 24 h of total intravenous urine reinfusion showed no change in renal NE content. Renal dopamine content was markedly increased in the UUO kidney, perhaps as a result of renal decarboxylation of dopa and failure of excretion, while renal and myocardial epinephrine content were increased in the BUO and urine reinfused groups, both of which were subjected to the stress of acute uremia. The decrease in renal NE content in the kidney undergoing postobstructive diuresis after relief of 24-h BUO probably indicates damage to sympathetic nerve terminals by high intrarenal pressure during BUO and suggests that partial renal denervation could contribute to the functional changes observed in this experimental model.