bluuebunny/crossref_metadata_2025 huggingface dataset:
Guar gum consumption in adolescent and adult rats: short- and long-term metabolic effects
Authors: Track Norman S. , Cawkwell Margaret E. , Chin Beth C. , Chiu Susan S. , Haberer Sean A. , Honey Christopher R.
Published: April 2011

Metabolic responses to short- and long-term guar gum consumption were studied in adolescent and adult rats. For the Song-term study, male adolescent rats were divided into four groups (n = 60/group) and fed guar gum, cellulose, or bran diet for 67 weeks. Metabolic studies (food–water intake, feces–urine output, body weight, carbohydrate tolerance) were performed eight times during the 67 weeks. The guar gum group consumed less diet throughout the entire study and gained less weight over the first 20 weeks compared with the cellulose and bran groups. A second bran-fed group was food restricted over the first 20 weeks to match the reduced weight gain of the guar gum group and then fed ad libitum. Reduced plasma glucose excursions were measured for only the guar gum group after both fibre-free glucose and sucrose challenges at weeks 6, 12, and 18; from 24 to 64 weeks all four groups had similar glucose tolerance responses. Twenty-four hour urinary glucose excretion was similar during all eight metabolic studies up to 64 weeks for guar gum and cellulose groups. In the short-term study, male adolescent (200 g; n = 10/group) and adult (630 g; n = 15/group) rats were divided into five and four groups, respectively, and fed guar gum, guar by-product (GBP), cellulose, or bran diet for 6 weeks. A metabolic study was performed during the 6th week. Adolescent rats fed guar gum or GBP diets gained less weight than the cellulose group; only the guar gum group displayed improved carbohydrate tolerance. Adult rats had similar weight gain and carbohydrate tolerance responses to the four diets. Both adolescent and adult rats fed GBP had significantly reduced 24-h urinary glucose excretion. These studies suggest that adolescent rats respond to guar gum consumption with reduced body weight gain and improved carbohydrate tolerance and demonstrate that these responses are lost or absent in adult rats.
Contribution of postexercise increment in glucose storage to variations in glucose-induced thermogenesis in endurance athletes
Authors: Tremblay Angelo , Fontaine Elizabeth , Nadeau André
Published: April 2011

The present study was undertaken to evaluate the contribution of an increment in glucose storage to the reduced glucose-induced thermogenesis (GIT) characterizing endurance-trained individuals. For that purpose, glucose storage and GIT were determined during an oral glucose tolerance test (OGTT) in eight elite endurance athletes exercising between 6 and 16 h/week. Their values were compared with those obtained in five nontrained subjects submitted to two OGTT, i.e., before and 16 h after they had performed a 90-min vigorous exercise. As expected, endurance athletes exhibited a reduced GIT and a greater glucose storage during the OGTT in comparison to the preexercise values of nontrained subjects. Once the latter subjects had performed the 90-min exercise, their glucose storage during the OGTT was similar to the level found in athletes. This adaptation was accompanied by a significant reduction in GIT, which corresponded to 47% of the difference observed between trained and nontrained subjects when both groups maintained their usual life habits. Unlike GIT, resting metabolic rate (RMR) was found to be higher in athletes than in nontrained individuals. When subdividing the athletes into two subgroups on the basis of the duration of their weekly training, it was found that RMR was mainly elevated in those performing the higher amount of exercise. These results demonstrate that the reduced GIT characterizing endurance-trained individuals is partly explained by an increase in glucose storage during an OGTT. As further discussed, this reduced GIT is likely an indirect consequence of modifications of other energy-requiring energy processes rather than a direct result of the postexercise increment in glucose storage.
Antagonism by theophylline of the adenosine receptor agonist 5′-N-ethykarboxamidoadenosine at the guinea pig ileum
Authors: Christofi F. L. , Cook M. A.
Published: April 2011

The inhibitory effect of the putative adenosine A2 receptor agonist 5′-N-ethylcarboxamidoadenosine (NECA) on acetylcholine release from the stimulated guinea pig ileum preparation and the nature of its antagonism by theophylline were investigated. NECA was shown to inhibit the response of the ileum preparation in a dose-dependent fashion, and an EC50 value of 1.62 × 10−8 M was determined. This value was comparable with that determined for the A1 receptor agonist N6-R-phenylisopropyladenosine (R-PIA) (2.57 × 10−8 M) using the same preparation. Competitive antagonism of the inhibitory effect of NECA by theophylline was quantitated and a pA2 value of 5.04 for the methylxanthine was obtained. This value was similar to those obtained previously for R-PIA and adenosine itself and suggests that these nucleosides may be interacting with the same receptor site on myenteric nerve endings. These findings do not permit the designation of the receptor as an A1 or A2 subtype according to current criteria.
The effects of pH on the kinetics of fatigue and recovery in frog sartorius muscle
Authors: Renaud J. M. , Mainwood G. W.
Published: April 2011

The effects of pH on the kinetics of fatigue and recovery in frog sartorius muscle were studied to establish whether the pH to which muscles are exposed (extracellular pH) has an effect on both the rate of fatigue development and recovery from fatigue. When frog sartorius muscles were stimulated with short tetanic stimuli at rates varying from 0.2 to 2.0 trains/s, a time- and frequency-dependent decrease in force development was observed, but extracellular pH had comparatively little effect. The recovery of tetanic force was dependent on the extracellular pH. This effect was characterized by a rapid recovery in force at pH 8.0 and an inhibition of recovery at pH 6.4 even when force decreased by only 25% during stimulation. Even when muscles were fatigued at pH 8.0 the rate of force recovery was still very small at pH 6.4. A model is proposed in which a step of the contraction cycle changes from a normal to a fatigued state. The rate of this transition is a function of the stimulation frequency and not pH. The reverse transition, from a fatigued to normal state is pH dependent; i.e., it is inhibited by H+. Measurements of resting and action potentials show that extracellular pH influences these parameters in the fatigue state, but there is no evidence that these changes are directly responsible for the pH-dependent step in the reversal of fatigue.
Changes in the cation composition and active K+ transport in the red cells of fetal sheep prepartum
Authors: Wolowyk M. W. , Ellory J. C.
Published: April 2011

The red blood cells of lambs, genotypically low potassium type, undergo a transition from high potassium to low potassium cell type from parturition onwards. This involves gradual changes in cell ion content, sodium pump activity, and ouabain binding. In the present study we investigated the properties of fetal red blood cells from 30 days prepartum using the chronically cannulated pregnant ewe preparation. We demonstrate that intracellular sodium increases and potassium decreases from −30 days onwards. Sodium pump activity monitored either by tracer potassium influx or ouabain binding is markedly higher in the early fetal samples examined and declines fourfold during the final month in utero. Unlike the maternal low potassium cells the early fetal red cells are refractory in terms of sodium pump stimulation by anti-L, the antibody in fact consistently inhibiting the pump. Finally, we have investigated the volume sensitivity and development of the ouabain-insensitive potassium fluxes in these cells and found that both fetal and maternal cells show a marked chloride-dependent, volume-sensitive passive potassium flux. We conclude that the decrease in active sodium transport between fetal red cells and adult low potassium cells is achieved partly by a reduction in the density of sodium pumps per cell, and then later by the introduction into the circulation of cells with Lp-antigen-modified sodium pumps.
Electromechanical characterization of the effects of racemic sotalol and its optical isomers on isolated canine ventricular trabecular muscles and Purkinje strands
Authors: Lathrop David A.
Published: April 2011

In both isolated canine ventricular trabecular muscle and Purkinje strand preparations, dl-sotalol and its two optical isomers d- and l-sotalol produced a concentration-dependent increase in action potential duration while other transmembrane electrical characteristics were not significantly affected. The magnitude of the increase in action potential durations was greater in Purkinje strand preparations. In Purkinje strand preparations, the effect was rate dependent (i.e., the increase in duration was proportionately greater when stimulation frequency was slowed). From the concentration of each compound calculated to produce a 50% maximal increase in Purkinje fiber action potential durations, d-sotalol appeared to be one to three times more potent than either l-sotalol or the racemate. Each compound appeared to increase force development in ventricular trabecular muscle preparations stimulated at a frequency of 2 Hz. Increased force development was only observed in Purkinje strand preparations stimulated at slower rates (0.5–0.33 Hz). These results are unlike those produced by other beta-adrenergic blockers and suggest that the antiarrhythmic effects of sotalol are related primarily to its effect of action potential duration. The estimated potency ratios established for the effect of dl-sotalol and its optical isomers on both trabeculae and Purkinkje fiber action potential durations (d > dl − l) may indicate that these effects are unrelated to the beta-adrenergic blocking properties of these compounds. The differential effect of sotalol on isolated trabeculae and Purkinje strand preparations may help to explain the clinically reported phenomenon of sotalol-induced torsade de pointes.
Effect of the calcium ionophore A23187 on superoxide generation in phorbol ester stimulated human neutrophils
Authors: Strnad Colette F. , Wong Kenneth
Published: April 2011

The calcium ionophore, A23187, and the tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), interacted synergistically to elicit an accelerated superoxide production response in human neutrophils. The lag period preceding PMA-induced superoxide generation was decreased in a dose-dependent manner by A23187 at a concentration range from 1.0 × 10−8 to 1.0 × 10−5 M. Superoxide production rate, however, was subject to biphasic effects. While the rate was potentiated in a dose-dependent manner at A23187 concentrations below 1.0 × 10−6 M, inhibitory influences became manifest at higher concentrations. Total superoxide production was subject to inhibitory effects, characterized by a mean inhibitory dose of 1.3 × 10−6 M. The synergistic interaction of A23187 with PMA is consistent with a role for protein kinase C in neutrophil activation. Inhibition at high A23187 concentrations appeared to result from the effects of elevated intracellular Ca2+ levels on either NADPH oxidase itself, or some step in the transduction process linking protein kinase C to the oxidase complex.
The effect of afterload on the cardiodepressor reflex response to coronary artery occlusion in dogs
Authors: Fallen E. L. , Beattie W. S. , Tait G. A.
Published: April 2011

The acute hemodynamic responses to anterior and posterior wall ischemia were examined at different afterloads in 30 open-chest anaesthetized dogs. Regional and global left ventricular responses to acute ischemia were also measured before and following bilateral cervical vagotomy in 18 dogs. As the preocclusion afterload (mean aortic pressure) was progressively raised with intravenous methoxamine, a significant decrease in stroke volume occurred following circumflex artery occlusion, whereas no change in stroke volume occurred following occlusion of the left anterior descending artery. Bilateral cervical vagotomy completely inhibited the decrease in stroke volume during circumflex occlusion at high afterload. Vagotomy had no effect on the hemodynamic response to acute anterior wall ischemia. Reversible cold vagal block in paced hearts at high afterload unmasked compensatory inotropy in the nonischemic anterior myocardial segment during circumflex occlusion. Restoring vagal tone by rewarming attenuated the fractional shortening of the nonischemic segment. The results indicate that a relationship exists between myocardial wall tension and reflex cardioinhibition during acute posterior wall but not anterior wall ischemia in dogs.
High performance liquid chromatography analysis of nifedipine and some of its metabolites in hypertensive patients
Authors: Snedden W. , Fernandez P. G. , Nath C.
Published: April 2011

Techniques are described for the analysis of nifedipine and three of its metabolites; dehydronifedipine (I), dehydronifedipinic acid (II), and dehydronifedipinolactone (III) in human serum and urine. The analytes are extracted at pH 9 or 3 with ethyl acetate and chromatographed on a C8 reverse-phase column. Recoveries from spiked control serum and urine ranged from 70 to 95% depending on the polarity of the analyte. The coefficient of variation ranged from 10 to 15% (nifedipine, I, and III at 50–200 ng/mL) and 15–20% (II at 200–2000 ng/mL). Accuracy was always within the limits of precision. The metabolism of nifedipine in a group of hypertensive patients receiving long-term nifedipine therapy was compared with that reported for acute administration. Serum nifedipine levels were comparable in both cases, but contrary to previous reports, dehydronifedipine was consistently found in significant amounts. Serum levels of II were considerably elevated but III was not detected either in serum or in urine. Thus, prolonged nifedipine therapy m conjunction with other antihypertensive medications appears to be associated with significant alterations in the metabolism of nifedipine compared with acute administration.
Effects of altered cholinergic function on working and reference memory in the rat
Authors: Beninger Richard J. , Wirsching B. A. , Jhamandas Khem , Boegman Roland J. , El-Defrawy Sherif R.
Published: April 2011

Many data suggest that the brain's cholinergic neurons participate in the control of memory and it has been suggested that cholinergic systems are involved differentially in working and reference memory. To test this hypothesis the effects on memory of unilateral injections of the neurotoxins, quinolinic acid or kainic acid into the cortically projecting cholinergic cells of the nucleus basalis magnocellularis (nbm) were evaluated. In experiment 1, quinolinate-injected (n = 7) and sham-operated (n = 7) rats were tested in a T-maze alternation task that requires working memory. Lesion rats performed significantly more poorly than shams and subsequent biochemical assays of cortical choline acetyltransferase (CAT) activity revealed significant reductions in the lesion rats. In experiment 2, kainate-injected (n = 9) and sham-operated (n = 8) rats were trained in an eight-arm radial maze with only four arms baited. Lesion rats made significantly more working memory errors (entries into baited arms from which the food had already been collected) than reference memory errors (entries into never baited arms). CAT assays showed that the lesion led to a decrease in cortical CAT with no significant change in hippocampal CAT. The results of these studies support the hypothesis that cholinergic neurons of the basocortical system may be differentially involved in working and reference memory.
Group III and IV receptors of skeletal muscle
Authors: Abrahams V. C.
Published: April 2011

The single largest group of sensory fibres leaving skeletal muscles are small myelinated or unmyelinated (groups III and IV) fibres. The receptors served by these small fibres have not been subjected to the same intensive study that receptors served by group I and II fibres have received. The evidence so far available suggests that receptors with group III and IV axons play a particular role in nociception and also subserve a wide range of sensory modalities. Despite their role in nociception, the primary afferent fibres from these receptors do not project to the substantia gelatinosa. A significant percentage of group III receptors are sensitive to stretch and have been thought to be the receptor source that initiates the clasp-knife reflex. Other group III receptors respond to chemical change within the muscle and have been implicated in the initiation of cardiovascular reflexes and the changes in muscle blood flow that accompany exercise. Group IV receptors also include high threshold mechanoreceptors and nociceptors. It is well known that encapsulated receptors are quite unevenly distributed within skeletal muscles and in different skeletal muscles. Preliminary evidence suggests that the variation in receptor content is not confined to encapsulated receptors, but that the receptors served by group III and IV afferents may have receptive properties that vary from muscle to muscle.
The noradrenaline content and innervation of brown adipose tissue in the young rabbit
Authors: Harris W. H. , Foster D. O. , Ma S. W. Y. , Yamashiro S. , Langlais-Burgess L. A.
Published: April 2011

This work examined the noradrenaline content of brown adipose tissue, the metabolic response to endogenous noradrenaline released during tyramine infusion, and the innervation of brown fat at the electron microscopic level in the young rabbit. The noradrenaline content (ng/g) of the interscapular and cervical fat deposits ranged from 256 ± 51 to 343 ± 59 and 399 ± 18 to 694 ± 92, respectively, in four groups of rabbits (1–2, 7–8, 12–13, and 25–27 days of age). There was considerable variation amongst animals in each age group, but no evidence of a major increase or decrease in noradrenaline content during the first 4 weeks of life. Intravenous infusion of tyramine (100 μg∙kg−1∙min−1) increased plasma noradrenaline concentration, oxygen consumption, and blood flow to brown fat. Thus noradrenaline released from endogenous sites, as well as injected noradrenaline, will initiate the thermogenic response of brown fat. Ultrastructurally, unmyelinated axons that were not organized in a fascicle were observed adjacent to the adipocytes in the late gestation fetus. By 1 week of age of axons were surrounded by Schwann cell cytoplasm which formed a fascicle. However, no evidence of myelination was found up to 21 days of age. Collectively, the data indicate that the brown adipocyte is fully responsive at 1–2 days of age even though myelination of the nerves is incomplete, and that the incomplete development of the sympathetic nerves at birth is not a factor in the synthesis of noradrenaline in the very young rabbit. In addition, brown fat of the newborn rabbit is not as thermogenically active as the brown fat of the cold-acclimated rat.
The effect of parasympathetic drugs on energy expenditure: relevance to the autonomic hypothesis
Authors: Dulloo A. G. , Miller D. S.
Published: April 2011

The influence of the parasympathetic nervous system in the control of energy expenditure was investigated in obese and lean rodents during chronic administration of drugs that alter parasympathetic transmission. In the genetically obese ob/ob mice and fa/fa rats and in monosodium glutamate induced hypothalamic obese mice, administration of the parasympathetic inhibitors hyoscine, benztropine, and mecamylamine either had no effect on energy balance or caused losses in body weight that could entirely be accounted for by a reduction in food intake; 24-h oxygen consumption in drug-treated animals was no different from that of the nontreated controls. In the lean animals, both the parasympathetic inhibitors (hyoscine, benztropine, and mecamylamine) and stimulators (bethanecol and neostigmine) had no influence on energy balance nor on body composition. These studies refute the concept that an overactive parasympathetic tone underlies the elevated energetic efficiency of obese models and suggests that the parasympathetic nervous system is unlikely to play an important role in the long-term control of energy expenditure.
14-β-Methyl-8-oxacyclorphan (BC-3016), a morphinan derivative with high affinity for kappa opioid receptor: comparison with dynorphin-A(1–13)
Authors: Lemaire Simon , Dumont Michel , Jolicoeur François , Belleau Bernard
Published: April 2011

14-β-Methyl-8-oxacyclorphan (BC-3016) was tested for its ability to depress the electrically evoked contractions of the guinea pig ileum (GPI) and of the mouse vas deferens (MVD) and to compete with the binding of prototype ligands selective for κ-, μ-, or δ-opioid receptors in membrane preparations of rat brain and guinea pig cerebellum. BC-3016 was a very potent agonist in the GPI and MVD preparations, with ID50 of 0.7 and 31 nM, respectively. The activity of levorphanol, a standard alkaloid related to BC-3016, was much lower in both assays with ID50 values of 44 and 86 nM, respectively. Conversely, the activity of BC-3016 was quite comparable to that of dynorphin-A(1–13) in both preparations. In the GPI assay, a putative κ-receptor antagonist, MR-2266, was 6.6 and 5.5 times more potent than naloxone in blocking the activity of BC-3016 and dynorphin-A(1–13), respectively. BC-3016 was also very potent in displacing bound [3H]ethylketocyclazocine ([3H]EKC) to membrane preparations of the guinea pig cerebellum, a brain component containing predominantly κ-opioid receptors (Ki of 0.58 nM). Its potency in the displacement of the bound μ-ligand, 3H-labelled (D-Ala2,MePhe4,Gly-OH5)-enkephalin ([3H]DAGO), to rat brain homogenates was somewhat lower (Ki of 0.8 nM) but still high when compared with its ability to displace the δ-ligand, 3H-labelled (D-Ser2, Thr6)-Leu-enkephalin ([3H]DSLET) to rat brain homogenates (Ki of 4.45 nM). The affinity of BC-3016 for the opioid receptor was 2.1-fold higher than that of U-50488H, a selective κ-opioid ligand. Finally, the relative potency of BC-3016 to bind each one of the receptor types was similar to that of dynorphin-A(1–13). These data indicate that the structural modifications of levorphanol leading to BC-3016 increases the affinity of the compound for the κ-opioid receptor and provides a compound whose profile of activity is similar in some respect to that of endogenous dynorphin-A(1–13).
Exercise suppression of thermoregulatory thermogenesis in warm- and cold-acclimated rats
Authors: Arnold Jeff , LeBlanc Jacques , Cote Jacques , Lalonde Josée , Richard Denis
Published: April 2011

An evaluation was made of the effects of an acute exercise bout on (i) nonshivering thermogenesis (NST) in cold-acclimated rats (4 °C for 6 weeks) and (ii) shivering thermogenesis in 24 °C-acclimated rats (24 °C for 6 weeks). Assessment techniques included indirect calorimetry during treadmill running and brown adipose tissue (BAT) mitochondrial guanosine diphosphate (GDP) binding immediately following a treadmill run. Calorimetric results for 24 °C-acclimated rats running at 4 °C indicated total substitution of shivering thermogenesis by exercise-derived heat. No difference in GDP-binding, an index of BAT nonshivering thermogenic activity, was observed between exercised and nonexercised 24 °C-acclimated rats. Calorimetric results for cold-acclimated rats running at 4 °C indicated a total suppression in the energy cost associated with NST, exercise-derived heat replacing or substituting for NST. Examining BAT properties in the exercised cold-acclimated rats revealed a significant 40% decrease in BAT mitochondrial GDP-binding. These results suggest that during running, metabolic heat due to the exercise (i) totally replaces shivering in 24 °C-acclimated rats and (ii) totally replaces BAT nonshivering thermogenesis in cold-acclimated rats.
Thermogenesis in response to various intakes of palatable food
Authors: LeBlanc Jacques , Lupien Diane , Diamond Pierre , Macari Marcos , Richard Denis
Published: April 2011

Complete energy balance studies were made on groups of overfed (A) and underfed (B) Wistar rats. In experiment A one group was fed cafeteria diet ad libitum (the intake was 29% larger than the control), two other groups were fed the same diet but in restricted quantities (18 and 9% above control), and a fourth group, fed a stock diet, served as control. In experiment B, caloric intake was restricted by 12 and 31% in two groups fed cafeteria diet, and by 21 and 34% in two other groups fed stock diet. The experiments lasted 41 days and during that period the protein gain was comparable between the control and the cafeteria-29% group (643.4 ± 33.3 vs. 578.1 ± 25.0) but the fat gain was significantly different between the two groups (863.2 ± 81.6 vs. 1663.2 ± 99.8 kJ). When energy expenditure (EE) (metabolizable energy less storage added to the cost of storage) is expressed as a percentage of metabolizable energy (ME) intake no significant difference was found among the groups. The average value was [Formula: see text]. This finding would not support the presence of dietary-induced thermogenesis in animals overfed on the cafeteria diet. However, since the obligatory cost associated with storing energy would not explain the higher EE of the overfed groups, it is suggested that the level of ME intake exerts continuous proportional regulatory action on EE and, as a result, energy is spared by underfeeding and it is wasted by overfeeding. Rats fed the cafeteria diet, independent of whether they are overfed or restricted were shown to increase both brown adipose tissue (BAT) protein content and thermogenic capacity in response to norepinephrine. For that reason it is suggested that it is not the caloric content of the diet which affects BAT but instead other factors such as fat content or palatability of the food. The results also suggest that BAT is not directly implicated in the regulatory responses associated with various intakes of food. Indeed in the underfed experiment, although the capacity of the BAT was enhanced in the cafeteria groups, the EE was not different from that of the animals fed the stock diet.
The ontogeny of placental Na+–K+ ATPase in the mouse and its impairment by ethanol
Authors: Kennedy L. A. , Mukerji S. , Elliott M. J.
Published: April 2011

We have investigated the normal ontogeny of Na+–K+ ATPase in the mouse placenta and the possibility that impairment in placental transport capacity, as reflected in reductions in NA+–K+ ATPase activity, is associated with alcohol-related embryonic growth restriction. We have demonstrated that over the normal course of pregnancy there is a dramatic increase in placental NA+–K+ ATPase activity which occurs in concert with the embryofetal body growth spurt. Maternal ethanol administration during the early period of placental enzymogenesis (days 7–9) resulted in a significant reduction (up to 40%) of placental Na+–K+ ATPase activity on day 15. Both the severity and the frequency of the reduction were dose dependent. The effect was associated with significant reductions in embryonic body and brain weight but no change in body length or prenatal mortality. Incubation of term placental fragments for 2 h in increasing concentrations of ethanol resulted in a comparable reduction in enzyme activity. Our studies demonstrate that direct ethanol exposure produces a reduction of placental Na+–K+ ATPase activity, that exposure during the early stages of enzymogenesis results in persistent reductions in Na+–K+ ATPase activity in the mature placenta, and that this effect is associated with deficits of embryonic body and brain growth. A direct causal relationship has not been proven; however, it is conceivable that the correlation between reduced placental Na+–K+ ATPase activity and impaired embryofetal growth reflects a common causal pathway.
Human group I excitatory projections from ankle dorsiflexors to quadriceps muscle
Authors: McIlroy W. E. , Brooke J. D.
Published: April 2011

A short latency projection of group I afferent fibers from ankle dorsiflexors to knee extensor muscles has been categorized as species specific to humans. However, the effects of the pathway have only been inferred from conditioning homonymous reflexes in relaxed muscle. This study focused directly on the responses evoked in the electromyogram of the heteronymous muscles when active, in two experiments. In the first, preferential activation of group I afferents of ankle dorsiflexors, by electrical stimulation of the common peroneal nerve, excited both vastus medialis (mean latency, 26.3 ms) and rectus femoris (mean latency, 33.5 ms). No excitation or inhibition in either muscle was associated with stimulation of the tibial nerve. The second experiment compared vastus medialis responses with common peroneal nerve stimulation during three different movement conditions in which the muscle was equally contracted: (i) rhythmic isotonic (pedalling), (ii) episodic isotonic, (iii) isometric contraction. Responses were identified in all three active states, with no significant differences in amplitude or latency. No responses were seen in the relaxed muscle.
Interactions of some partial agonists with high and low affinity binding sites in β-adrenoceptors
Authors: Takayanagi I. , Koike K. , Nakagoshi A.
Published: April 2011

Interactions of derivatives of befunolol (BFE-37, BFE-55, and BFE-61), carteolol, and pindolol with β-adrenoceptors were tested in guinea pig isolated taenia caecum. All the drugs used acted as partial agonists on the β-adrenoceptors when compared with isoprenaline, a full agonist. The pA2 values of BFE-61, carteolol, and pindolol were significantly larger than their pD2 values, while there was no significant difference between the pA2 and pD2 values for BFE-37 and BFE-55. The specific binding of [3H]befunolol to microsomal fractions from the guinea pig taenia caecum distinguished two binding sites, high affinity and low affinity sites. Both sites are considered to be bound by 50 nM of [3H]befunolol. Specific 3H binding was displaced by BFE-61, carteolol, and pindolol in a biphasic manner but in a monophasic manner by BFE-37 and BFE-55. Furthermore, [3H]befunolol binding was only partially displaced by BFE-55 but completely displaced by the other drugs used. These results, together with our previous findings, suggest that BFE-61, carteolol, and pindolol discriminate between the two affinity binding sites in the β-adrenoceptors, which are not discriminated between by BFE-37, and further that BFE-55 may bind with only the high affinity site.
Effect of cholera toxin on triacylglycerol lipase activity and triacylglycerol content of rat heart
Authors: Miller W. C. , Palmer W. K. , Arnall D. A. , Oscai L. B.
Published: April 2011

This study was performed to reexamine the effect of cholera toxin on total and intracellular alkaline lipoprotein lipase (LPL) activity in rat heart. In addition, the relationship between intracellular triacylglycerol (TG)lipase activity and TG content of cardiac tissue was determined in cholera toxin treated rats. One intravenous injection of cholera toxin increased total LPL activity significantly above control activity 4 h following treatment. After 16 h, total enzyme activity in hearts of cholera toxin treated rats was 2.4-fold above control levels and remained significantly above the control activity up to the 24-h time point. Intracellular alkaline TG lipase activity was increased 24%, 59%, 2.1-fold, and 2.1-fold above control levels measured 0.5, 8, 16, and 24 h following cholera toxin treatment, respectively. Heart TG content fell significantly following cholera toxin treatment, with a maximal reduction seen 8 h following agent injection. At that time, TG was 0.61 μmol/g, a reduction of 63% below the control concentration of 1.8 μmol/g. A negative relationship between myocardial intracellular TG lipase activity and TG concentration of r = −0.83 was highly significant (P < 0.001). These findings indicate that cholera toxin injection can increase total cardiac LPL activity and show that 70% of this increased activity is in the intracellular fraction. The highly significant relationship between enzyme activity and TG content support our working hypothesis that the intracellular alkaline TG lipase (LPL) is playing a role in regulating cardiac TG content.
Substrate supply for thermogenesis induced by the β-adrenoceptor agonist BRL 26830A
Authors: Wilson S. , Thurlby P. L. , Arch J. R. S.
Published: April 2011

The nature of the substrate that fuels the thermogenic response to the novel β-adrenoceptor agonist BRL 26830A has been investigated. Respiratory quotient measurements indicated that the increase in metabolic rate produced by BRL 26830A in rats was fuelled wholly by lipid. BRL 26830A also produced a marked reduction in the lipid content of total dissectable brown adipose tissue. The energy content of this lipid lost during the 4-h period after dosing was equivalent to approximately 50% of the thermogenic effect of the compound over the same period, suggesting that lipid stored in brown adipose tissue is a major initial fuel for BRL 26830A induced thermogenesis. However, marked depletion of brown adipose tissue lipid prior to administration of BRL 26830A had no effect on the subsequent thermogenic response to the compound. Oral administration of glucose altered the pattern of fuel utilization for resting metabolism, but thermogenesis was still fuelled mainly by lipid. Administration of methyl palmoxirate, which inhibits oxidation of long-chain fatty acids, completely prevented the thermic effect of BRL 26830A, suggesting that lipid is a necessary fuel for this process. These results do not support suggestions that carbohydrate is quantitatively important as a fuel for nonshivering thermogenesis.
Effects on the murine mononuclear phagocyte system of chronic administration of liposomes containing cytotoxic drug or lipid A compared with empty liposomes
Authors: Allen T. M. , Murray L. , Alving Carl R. , Moe James
Published: April 2011

In experiments designed to examine the adverse effects of chronic liposome administration in vivo on the mononuclear phagocyte system (reticuloendothelial system), the presence of drug entrapped in the liposomes may increase the level of reticuloendothelial impairment. We have compared the effects on the mononuclear phagocyte system in mice of chronic administration of empty liposomes with the effects of liposomes containing the anti-leishmanial drug meglumine antimoniate. We have also examined the effect on the mononuclear phagocyte system of continued injections of liposomes containing lipid A, a component of bacterial lipopolysaccharide, which is responsible for macrophage activation. Ten intravenous injections of multilamellar liposomes composed of dipalmitoylphosphatidylcholine and cholesterol (1:0.75 M ratio) were given to ICR mice over a 25-day period. Two individual groups of mice received endotoxin-free liposomes in which meglumine antimoniate was either present or absent. One addition group received liposomes containing lipid A derived from Escherichia coli lipopolysaccharide. A control group received sterile saline injections. In each group, a depression of the phagocytic index, as measured by reduction of uptake of particulate carbon, was observed among some of the individual animals 24 h after the first injection. In many mice a marked splenomegaly was observed. A depressed phagocytic index and splenomegaly were most marked for mice receiving lipid A liposomes. However, there was a large individual variability among mice receiving these preparations and some mice in each group had normal spleen size and a nearly normal phagocytic index. Tissue distribution of liposomes containing [14C]dipalmitoylphosphatidylcholine as a phospholipid marker was examined in all groups in mice 24 h after the last injection. Mice receiving liposomes with entrapped meglumine antimoniate showed decreased liver and increased spleen uptake of radiolabel as compared with controls. This has previously been suggested to be an indication of reticuloendothelial blockade. Mice receiving liposomes without meglumine antimoniate had tissue distributions of liposomes similar to control mice, and mice receiving liposomes containing lipid A had greatly decreased spleen uptake and increased liver uptake of liposomes as compared with control mice and mice receiving endotoxin-free liposomes (an indication of reticuloendothelial stimulation), suggesting that liposomes are being treated differently from particulate carbon in the presence of lipid A.
Desensitization of isolated smooth muscle cells from guinea pig taenia caecum to acetylcholine
Authors: Mita Mitsuo , Uchida Masaatsu K.
Published: April 2011

The role of tissue organization of smooth muscle in short-term desensitization to acetylcholine (ACh) was examined by studying the desensitization of isolated single cells from guinea pig taenia caecum. Cells were isolated by collagenase digestion. The conditions during cell isolation were adjusted to obtain cells that showed repeated contractions. The cells contracted on treatment with 10−7–10−6 M ACh, showing an all-or-none response. Desensitized cells also showed an all-or-none response but required a higher concentration of ACh for induction of contraction; i.e., the magnitude of their maximal response was not changed appreciably but the threshold concentration of ACh for their contraction was raised. Incubation of the whole tissue with 10−4 M ACh for 10 min also caused desensitization. This desensitization was accompanied by reduction of the contractile response at intermediate concentrations. The mode of desensitization of isolated cells determined from the average response of the isolated cells was almost the same as that of whole muscle. It is concluded that the desensitization occurred in each cell irrespective of its tissue organization and that the desensitization was due to an increase of the threshold for contraction to ACh of each cell.
Left ventricular rupture threshold during the healing phase after myocardial infarction in the dog
Authors: Jugdutt Bodh I.
Published: April 2011

The mechanical resistance of the infarcted left ventricle to rupture, or rupture threshold, was measured by the balloon technique 1–42 days after left anterior descending coronary artery ligation in 70 dogs: 26 without infarction (18 sham, 8 with ligation) and 44 with infarction. Rupture threshold in noninfarcted hearts was higher than in infarcted hearts (1168 ± 165 (SD) vs. 754 ± 223 mmHg (1 mmHg = 133.32 Pa), p < 0.001) and did not change over 6 weeks. In contrast, rupture threshold in infarcted hearts decreased (p < 0.05) after 14 days, the average value for 21–42 days being less than that for 1–14 days: 577 ± 140 vs. 867 ± 191 mmHg, p < 0.001. Passive left ventricular stiffness in infarcted hearts was higher than for noninfarcted hearts throughout the 6 weeks during early filling (11.1 ± 3.9 vs. 7.1 ± 1.4 mmHg/mL, p < 0.001) but decreased (p < 0.05) after 14 days during the prerupture phase (11.3 ± 5.3 vs. 6.2 ± 3.0 mmHg/mL, p < 0.005). Between 7 and 42 days, the infarct zone showed marked increase in hydroxyproline (10.0 ± 2.0 vs. 48.8 ± 19.7 mg/g dry weight, p < 0.001), shrinkage (infarct size, 25 ± 9 vs. 9 ± 5% of the left ventricle, p < 0.005), and thinning (infarct to normal wall thickness ratio, 0.83 ± 0.11 vs. 0.51 ± 0.09, p < 0.001) but little further stretching (expansion index or the ratio of lengths of infarcted and noninfarcted segments, 1.14 ± 0.10 vs. 1.28 ± 0.17, p < 0.2). A mild decrease (p < 0.05) in left atrial pressure and increase (p < 0.05) in diastolic area and fractional change in area (two-dimensional echocardiography) were detected at 6 weeks. The late decrease in rupture threshold and prerupture stiffness of the infarcted left ventricle and thinning of the scar suggest a late decrease in mechanical strength and resistance of the infarcted left ventricle to distension.
Definition of subclasses of adenosine receptors associated with adenylate cyclase: interaction of adenosine analogs with inhibitory A1 receptors and stimulatory A2 receptors
Authors: Ukena Dieter , Olsson Ray A. , Daly John W.
Published: April 2011

The structure–activity relationships of 63 adenosine analogs as agonists for the A1 adenosine receptors that mediate inhibition of adenylate cyclase activity in rat fat cells and for the A2 adenosine receptors that mediate stimulation of adenylate cyclase in rat pheochromocytoma PC12 cells and human platelets were determined. The lack of correspondence between the structure–activity relationships of these analogs at the A1 and A2 receptors appear definitive in terms of establishing the existence of A1 and A2 subclasses of adenosine receptors. However, significant differences in the agonist profiles at A2 receptors of platelet and PC12 indicate a certain degree of structural heterogeneity within the members of the A2 adenosine receptor subclass. Whether such differences are due to different species or different cell types is not known. A set of adenosine analogs, such as N6-cyclohexyl-, N6-R-, and S-1-phenyl-2- propyladenosines, 5′-N-ethylcarboxamidoadenosine and its N6-cyclohexyl derivative, 2-chloro- adenosine, and 2-phenylaminoadenosine, appear to represent a series of analogs useful for pharmacological characterization of A1 and A2 classes of adenosine receptors.
Effect of chlorpromazine on the synthesis, hydrolysis, and transfer of microsomal cytidine liponucleotides and mitochondrial polyglycerophosphatides
Authors: Stuhne-Sekalec L. , Chudzik J. , Stanacev N. Z.
Published: April 2011

The effect of chlorpromazine on subcellular biosynthesis, hydrolysis, and transfer of lipids and liponucleotides participating in the biosynthesis of polyglycerophosphatides in guinea pig liver was studied. Chlorpromazine showed an apparent stimulation of accumulation of phosphatidic acid and CDP-diglycerides in microsomal membranes and phosphatidylglycerolphosphate in mitochondrial membranes in a concentration-dependent manner that was influenced by incubation time and the nature of fatty acids in CDP-diglycerides. Transfer of membrane-bound CDP-diglycerides from microsomal to mitochondrial membranes was established by the CDP-diglyceride-dependent biosynthesis of phosphatidylglycerolphosphate and phosphatidylglycerol and appeared to be inhibited by the addition of chlorpromazine by about 20%. Evidence was obtained for the formation of a molecular complex between phosphatidic acid and chlorpromazine; this was thought to be responsible for the protection from phosphatidate phosphohydrolase at the concentrations of chlorpromazine and Mg2+ examined.
Potentiation of the responses to transmural nerve stimulation by α-agonists: a possible role in vivo
Authors: Senaratne M. P. J. , Jayakody R. L. , Kappagoda C. T.
Published: April 2011

This study was undertaken to assess the effects of exogenous α-agonists on the effector response to transmural nerve stimulation in canine saphenous vein rings. The response to a fixed train (5 s duration) of transmural nerve stimulation (8 Hz, 0.3 ms, 9 V) applied every 5 min was determined in the control state and in the presence of subthreshold (for contraction) concentrations of noradrenaline, adrenaline, clonidine, and methoxamine. The maximum potentiations achieved by the three drugs were 246.2 ± 36.9, 220.5 ± 38.8, 384.3 ± 78.7, and 353.3 ± 68.0%, respectively. The potentiation observed was significantly inhibited by indomethacin (10−6 mol/L) and propranolol (5 × 10−6 mol/L). Both indomethacin and propranolol potentiated the response to transmural nerve stimulation. The potentiation of the responses to transmural nerve stimulation by α-agonists suggests that, presynaptic α2-inhibition by circulating catecholamines is likely to be of limited biological significance in modulating the effector responses in the canine saphenous vein.
The interaction of histamine with other bronchoconstrictor mediators
Authors: Burka J. F.
Published: April 2011

The lack of therapeutic efficacy of antihistaminic drugs in the treatment of asthma has led to the search and discovery of other bronchoconstrictor agents, particularly leukotrienes, thromboxanes, and platelet-activating factor. However, specific receptor antagonist for any of these substances have also not been particularly effective in inhibiting allergic bronchoconstriction. It is now generally accepted that histamine, arachidonic acid metabolites, platelet-activating factor, and possibly other substances are all involved to varying degrees in asthma and may indeed interact. This paper reviews the interaction of these mediators and how they contribute to airway hyperreactivity.
Activation of skinned muscle fibers by calcium and strontium ions
Authors: Goblet C. , Mounier Y.
Published: April 2011

Intact and mechanically skinned skeletal muscle fibers of the crab Carcinus maenas have been used. The aim of the experiments was to determine the origin of the mechanical activity recorded in intact crab muscle fibers exhibiting an inward strontium current in strontium solution without calcium. To do so, the effect of strontium ions in inducing activation of contractile proteins and calcium release from the sarcoplasmic reticulum has been studied. The properties of the sarcoplasmic reticulum membrane towards strontium ions, i.e., the efficiency of the calcium ATPase towards strontium ions and the capability to release strontium ions have been investigated. Results show that the contractile proteins have a lower affinity for strontium than for calcium ions. However, the maximum bound strontium is identical to the maximum bound calcium. As for the sarcoplasmic reticulum, strontium ions can induce a calcium release and also can be taken up by the calcium ATPase and be released. We concluded that the mechanical activity in intact fibers bathed in a strontium medium has two origins: first, a direct and partial activation of the contractile proteins by strontium ions flowing through the calcium channel; second, a contractile proteins activation of calcium ions released by the sarcoplasmic reticulum by a "strontium-induced calcium release" mechanism.
Effects of repetitive activity, ruthenium red, and elevated extracellular calcium on frog skeletal muscle: implications for t-tubule conduction
Authors: Howell John N. , Oetliker Hans
Published: April 2011

In this report we review evidence that indicates that experimental elevation of t-tubular calcium can lead to failure of action potential propagation within the t system and we present some new evidence suggesting that t-tubular calcium concentration may rise during repetitive activity. The evidence for t-tubular conduction failure consists of comparisons of the effects of high calcium and of ruthenium red on excitation and excitation–contraction coupling as well as morphological observations of wavy myofibrils in the axial core of fibers contracting tetanically in solutions containing elevated calcium concentrations. Evidence for elevation of t-tubular calcium concentration during repetitive activity comes from the following. During twitches, the early, large birefringence signal and force development arc delayed in onset if the extracellular calcium and (or) potassium concentrations are above normal or if the fiber has been stimulated tetanically just prior to the test twitch. The delays that occur in twitches following tetanic contractions are attenuated when the extracellular and, therefore, the t-tubular calcium concentration is buffered with citrate.