bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of diazepam on potassium contractures, contraction threshold, and resting tension in rat skeletal muscles
Authors: Chua Michael , Dulhunty Angela F.
Published: April 2011

The effects of diazepam on potassium contractures, contraction threshold, and resting tension have been examined in rat soleus muscle fibres. Two actions of the drug were defined that could not be attributed to changes in the resting membrane potential or depolarization in high potassium solutions. The major effect was an increase in the amplitude of submaximal tension during either twitches or potassium contractures and an increase in resting tension. At 400 μM diazepam, there was (a) a fourfold increase in 40 mM potassium contracture tension, (b) a negative shift of 8 mV in the membrane potential for half maximum tension estimated from the best fit of a Boltzmann-type equation to average potassium contracture data, (c) a negative shift of 8 mV in the threshold for contraction measured under voltage clamp conditions, and (d) a contracture of variable amplitude to a level that was occasionally equivalent to maximum tetanic tension. These potentiating actions of diazepam depended on drag concentration within the range of 100–800 μM. In contrast, the second effect of diazepam, depression of maximum tension by 10–15%, was independent of drug concentration between 100 and 400 μM. The results support the idea that diazepam produces an increase in resting myoplasmic calcium concentrations.
Exercise and postexercise energy expenditure in growing pigs
Authors: Petley Mary Pat , Bayley Henry S.
Published: April 2011

Young pigs (ca. 10 kg) were trained to run on a motor-driven treadmill for 1 h each day. After a 2-week training period the gas exchange of exercised and control animals was measured using an open circuit, indirect calorimeter. The exercised pigs ran for 2 h in the calorimeter, and then rested for 2 h. They received a day's allocation of feed and remained in the calorimeter for a total of 23 h. The total heat production of the exercised pigs was 523 kJ/kg, compared with 433 kJ/kg of the controls. Monitoring the heat production throughout the 23-h period showed that only 43% of the extra heat dissipated by the exercised pigs was lost during the 2 h of exercise, with a higher rate of heat production for the remaining 21 h accounting for the 57% of the extra energy dissipated as heat. The results suggest that exercise increases energy expenditure well beyond the time devoted to the activity itself.
The action of epidermal growth factor on human amnion prostaglandin E2 output
Authors: Zakar Tamas , Olson David M.
Published: April 2011

The mechanism of stimulatory action of epidermal growth factor on term human amnion prostaglandin E2 production was studied. Monolayer cultures of amnion epithelial cells from spontaneous vaginal deliveries were preincubated for 24 h with serum-free media and treated with epidermal growth factor, calcium ionophore A23187 (4.5 μM), and arachidonate. Cumulative prostaglandin E2 output was not stimulated by epidermal growth factor (≤200 ng/mL) or A23187 alone or the two added together. Pretreating the cells with epidermal growth factor for at least 2 h followed by A23187 or arachidonate (in the continuing presence of epidermal growth factor), however, stimulated prostaglandin E2 output up to 14-fold. The maximum effect of epidermal growth factor was attained at 1–10 ng/mL, while the EC50 was 0.2–0.32 ng/mL. Ionophore- or arachidonate-promoted prostaglandin E2 output was not stimulated by pretreatment with platelet-derived growth factor, fibroblast growth factor, and β-transforming growth factor. Cycloheximide added before, at the same time as, or up to 30–60 min after epidermal growth factor completely abolished the stimulation. Epidermal growth factor did not affect [14C]arachidonate incorporation into cells or cell lipids. These results suggest that epidermal growth factor promotes, specifically and in a protein synthesis dependent manner, the conversion of arachidonate to prostaglandin E2. The provision of exogenous or endogenously liberated arachidonate is also necessary for enhanced amnion prostaglandin E2 production.
Effect of Desmodium adscendens fractions on antigen- and arachidonic acid-induced contractions of guinea pig airways
Authors: Addy Marian E. , Burka John F.
Published: April 2011

Three fractions (n-butanol, F2, and L5), isolated from an aqueous extract of Desmodium adscendens, a plant used in Ghana for the management of asthma, were evaluated for their pharmacological activity using ovalbumin and arachidonic acid-induced contractions of guinea pig airways. All three fractions inhibited the ovalbumin-induced contractions of indomethacin-pretreated tracheal spirals from sensitized animals dose dependently, but only L5 and n-butanol inhibited such contractions in the absence of indomethacin. The concentrations required to inhibit ovalbumin-induced contractions of lung parenchymal strips were threefold higher than with trachea. The contractile response over a 60-min period was divided into three phases. F2 and n-butanol inhibited all phases, whereas L5 inhibited only the late phase. n-Butanol and L5 inhibited arachidonic acid-induced contractions on indomethacin-pretreated tracheal spirals, a leukotriene-dependent reaction. There was no inhibition of arachidonic acid-induced contractions of lung parenchymal strips, which is largely a thromboxane-dependent reaction. The results suggest that D. adscendens contains several pharmacologically active substances that can inhibit allergic airway smooth muscle contraction at multiple sites, including the synthesis and (or) activity of the bronchoconstrictor leukotrienes.
The involvement of nonspiking cells in long-term potentiation of synaptic transmission in the hippocampus
Authors: Sastry B. R. , Goh J. W. , May P. B. Y. , Chirwa S. S.
Published: April 2011

In guinea pig hippocampal slices, stimulation of stratum radiatum during depolarization (with intracellular current injections) of nonspiking cells (presumed to be glia) in the apical dendritic area of CA1 pyramidal neurons resulted in a subsequent long-term potentiation of intracellularly recorded excitatory postsynaptic potentials as well as extracellularly recorded population spikes in the CA1 area. Tetanic stimulation of stratum radiatum resulted in a subsequent prolonged depolarization of the presumed glial cells, and this depolarization was smaller when the tetanus was given during the presence of 2-amino-5-phosphonovalerate or when the slices were exposed to Ca2+-free medium containing Mn2+ and Mg2+. These results suggest that glial depolarization is involved as one of the steps in generating long-term potentiation.
Membrane responses of neurons in human sympathetic ganglia
Authors: Puil E. , El-Beheiry H. , Spigelman I.
Published: April 2011

Electrophysiological studies were performed on in vitro slice preparations of sympathetic ganglia excised from peripherally perfused, brain-dead human donors. The intracellular recordings in 16 neurons showed resting potentials and input resistances mostly in the ranges reported for sympathetic neurons in other mammals. The high input resistances (~29 MΩ) can account for the long membrane time constants measured in three neurons [Formula: see text]. Spikes that were part of anodal break responses as well as those evoked by current pulse injections were tetrodotoxin sensitive and were more prolonged in duration by tetraethylammonium than by 4-aminopyridine applications. Administrations of isoflurane (0.5–2 minimum alveolar concentrations) by perfusion did not greatly affect the membrane properties, but produced a marked reduction in repetitive spike firing evoked by current pulse injections as well as in the postspike afterhyperpolarizations, suggesting that a sympathetic neurogenic mechanism may contribute to the hypotension observed clinically during isoflurane anaesthesia. These investigations demonstrate for the first time that human sympathetic ganglion neurons can be studied successfully in in vitro preparations, and hence are valuable for direct relevance to the human condition.
Alteration in sialidase and other glycosidase activities in the kidney of spontaneously hypertensive rats: persistence after preventive treatment with hydralazine
Authors: Cohen-Forterre L. , Grigorova-Borsos A. M. , Falcy C. , Mansour G. , Mozere G. , Peyroux J. , Sternberg M.
Published: April 2011

Because kidney microangiopathy with capillary basement membrane thickening has been reported in spontaneous hypertension, we have studied the activities of three lysosomal glycosidases able to degrade the carbohydrate moieties of basement membrane constituents in the kidney cortex of 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). These activities were also determined in SHR and WKY treated from 6 to 12 weeks of age with hydralazine (mean dose, 18 mg/kg per day in drinking water). Sialidase specific activity on sialyl-α2-3-[3H]lactitol was markedly decreased in the kidney of untreated SHR, 40% activity remaining relative to that found in untreated age-matched WKY (p < 0.001). β-Galactosidase specific activity on p-nitrophenyl-β-D-galactoside was also decreased, 86% activity remaining relative to that found in untreated WKY (p < 0.001). Glucosyl-galactosyl-hydroxylysyl glucohydrolase specific activity on glucosyl-galactosyl-hydroxylysine was equally diminished, 74% activity remaining relative to that found in untreated age-matched WKY (p < 0.001). In contrast, the activities of two control glycosidases inactive on the carbohydrate moieties of basement membrane constituents, α-glucosidase assayed with p-nitrophenyl-α-D-glucoside as substrate and β-glucosidase assayed with p-nitrophenyl-β-D-glucoside as substrate, were significantly increased. All the alterations in enzyme activities observed in the kidney of SHR were also present in the long-term treated normotensive SHR. No effect of the hydralazine treatment on the three enzyme activities investigated could be demonstrated in the WKY. Thus the alterations observed in the kidneys of SHR appear to be independent of blood pressure level.
Release of exogenously supplied [3H]glutamate and endogenous glutamate from tissue slices of the cestode Hymenolepis diminuta
Authors: Webb Rodney A.
Published: April 2011

The effect of high potassium depolarization on the release of exogenously supplied [3H]glutamate and endogenous glutamate from tissue slices of the cestode Hymenolepis diminuta was examined. Increasing concentrations of potassium stimulated the release of radiolabel from tissues preloaded with [3H]glutamate. This release was by a partially calcium-dependent, magnesium-antagonized process. In the presence of tetrodotoxin, or absence of sodium, release of radiolabel was depressed, presumably by blockade of sodium-dependent neuronal potentials. The release of glutamate of both exogenous and endogenous origin was specifically and significantly elevated by high potassium; glutamate release was significantly depressed in calcium-free saline. The release of other amino acids of endogenous origin, including aspartate, was not elevated by high potassium. Collectively the data provide strong evidence for glutamate to be viewed as the only acidic amino acid neurotransmitter candidate in the cestodes.
The abnormal mechanical strength–interval curve of hypoxic rabbit papillary muscle
Authors: Goodyer Allan V. N.
Published: April 2011

The effect of hypoxic injury on the mechanical strength–interval curve of rabbit myocardium was studied, using an isolated left ventricular thick papillary muscle preparation. Histochemical staining disclosed a central core of injured tissue enveloped by viable muscle which was sustained by aerobic metabolism, being unaffected by iodoacetate. Mechanical strength–interval curves were derived by measurement of developed isometric tension during various pacing protocols. The phasic recovery of contractile tension, described by the strength–internal curve, was markedly prolonged and partly responsible for reduced tension development. Parameters of the strength–interval curve were determined by linear and monoexponential curve-fitting procedures during various experimental interventions. These parameters indicated that the contractility recovery rate was not altered by acidosis or propranolol, but the early phase of the strength–interval curve (at short test intervals) was augmented by propranolol, and the plateau of the full curve was depressed by acidosis. These observations emphasize that the strength–interval curve must be considered in any study of the effect of a drug or other intervention on the contractility of hypoxic myocardium.
Glycogen utilization in rat respiratory muscles during intense running
Authors: Green Howard J. , Ball-Burnett M. E. , Morrissey M. A. , Kile J. , Abraham G. C.
Published: April 2011

Glycogen concentration in the adult rat diaphragm and intercostal muscles has been examined following heavy treadmill exercise to determine the recruitment strategy and the significance of glycogen as a substrate to satisfy the elevated energy requirements accompanying hyperpnea. Short-term continuous running at 60 m/min and a 12° grade resulted in a reduction (p < 0.05) in the concentration of glycogen (39%) in the costal region of the rat diaphragm. Similarly, glycogen concentration was significantly reduced (p < 0.05) with this exercise protocol in all respiratory muscles studied, with the exception of the sternal region of the diaphragm. With the less intense running protocols, glycogen degradation continued to be pronounced (p < 0.05) in the majority of the respiratory muscles sampled. The significance of muscle glycogen as a substrate for energy metabolism in the respiratory muscles was not affected by the procedure used to prepare the animal for tissue sampling (Somnitol, diethyl ether, decapitation). Examination of selected locomotor muscles revealed extensive glycogen loss in muscles composed of essentially slow oxidative fibres (soleus), fast oxidative glycolytic fibres (vastus lateralis red), and fast glycolytic fibres (vastus lateralis white). It is concluded that during heavy exercise in the rat, recruitment of motor units occurs in all regions of the diaphragm and in the intercostal muscles. At least for the costal region of the diaphragm and as evidenced by the modest (two- to four-fold) but significant (p < 0.05) increases in lactate concentration, the increased ATP requirements in these muscles are met to a large degree by increases in aerobic metabolism. It is concluded that endogenous glycogen is an important substrate for energy metabolism during intense running in both the respiratory and locomotor muscles regardless of fibre composition.
Atrial natriuretic factor alters autonomic interactions in the control of heart rate in conscious rats
Authors: Ackermann Uwe , Khanna Julie , Irizawa Terumi G.
Published: April 2011

Regulation of heart rate was studied in rats receiving either i. v. saline at 64 μL/min or synthetic 28-residue rat atrial natriuretic peptide (ANF) at a dose sufficient to decrease mean arterial blood pressure by 10%. Autonomic influences were deduced from steady-state heart rate responses of each group to propranolol, atropine, or propranolol and atropine combined. A multiplicative model of heart rate control was used to derive quantitatively from the data the modulation of intrinsic heart rate by sympathetic and parasympathetic mechanisms. Animals receiving ANF showed a lower heart rate than control animals. This relative bradycardia was abolished by atropine. Blocking of sympathetic effects with propranolol had no effect on basal heart rate in either group, and atropinization led to significant increases in heart rate in both groups of rats. Mathematical analysis of the results showed that the bradycardia produced by ANF was due predominantly to a reduced intrinsic heart rate and to enhanced vagal inhibition of postganglionic sympathetic activity. Parasympathetic contribution to heart rate in the absence of sympathetic activity was negligible in control rats and small during ANF. We conclude that the major influences of ANF on heart rate control are a decrease of intrinsic heart rate and enhanced parasympathetic inhibition of postganglionic presynaptic sympathetic activity.
Atrial natriuretic peptide interferes with calcium requirements in vascular tissues of the rat
Authors: St-Louis Jean , Coderre Céline , Schiffrin Ernesto L.
Published: April 2011

The inhibitory effect of atrial natriuretic peptide on the myotropic action of phenylephrine on superior mesenteric artery and thoracic aorta rings was studied to test the hypothesis that this peptide interferes with the mobilization of intra- or extra-cellular calcium produced by vasoconstrictor agents. In the absence of calcium in the bathing solution, phenylephrine (10−6 M) produced a residual effect, which was antagonized in a concentration-dependent manner by the atrial peptide in both mesenteric artery and aorta rings. When calcium (2.5 mM) was added to the bathing solution after the response to phenylephrine in the absence of calcium, a further increase in the tonus of the tissue was observed. This effect was also antagonized by atrial natriuretic peptide in a dose-dependent manner in the two tissues. These results suggest that atrial natriuretic peptide inhibits the effect of vasoconstrictor agents by functionally interfering with the mobilization of intra- and extra-cellular calcium produced by these vasoconstrictors.
Neuronal nicotinic α-bungarotoxin sites
Authors: Quik M. , Geertsen S.
Published: April 2011

At the vertebrate neuromuscular junction and in the electroplax of eel and electric fish, the nicotinic α-bungarotoxin site and the nicotinic receptor involved in synaptic transmission are very tightly coupled and, indeed, appear to be the same molecular component. On the other hand, the nature of the relationship between the nicotinic receptor mediating synaptic events and the nicotinic α-bungarotoxin binding site in nervous tissue has been a matter of controversy over the last few years. Experimental studies have been accumulating which suggest that in many neuronal tissues these two components are distinct molecular entities with their own unique regulation. However, it also appears that in other nervous tissues, possibly in species lower on the evolutionary scale, the toxin binding site is part of the nicotinic receptor. An evaluation of all available evidence would point to the conclusion that, in neuronal tissues, the nicotinic acetylcholine receptor involved in synaptic events and the nicotinic α-bungarotoxin site can exist both in a tightly coupled form and one in which the two sites are mutually distinct. The possible physiological significance of the nicotinic α-bungarotoxin site is discussed in light of current experimental data. Evidence is available which may imply that the α-toxin site, whether it is present as a distinct entity or in association with the nicotinic acetylcholine receptor, is involved in trophic or growth related activities, as well as in other cellular functions. The possibility of an endogenous ligand for the nicotinic α-bungarotoxin site is also discussed.
The effect of dietary protein and sulfur amino acids on hepatic glutathione concentration and glutathione-dependent enzyme activities in the rat
Authors: Bauman P. F. , Smith T. K. , Bray T. M.
Published: April 2011

Hepatic glutathione concentration and glutathione-dependent enzymes, glutathione S-transferase, glutathione peroxidase, and glutathione reductase, are important for protection against toxic compounds. Rats were fed diets containing 4, 7.5, 15, or 45% protein for 2 weeks. Glutathione and cysteine concentrations in rats fed the 4 and 7.5% protein diets were significantly lower (p < 0.05) than in rats fed the 15 and 45% protein diets. Glutathione S-transferase activity increased with increasing dietary protein. Glutathione peroxidase activity was significantly lower (p < 0.05) in rats fed 4 and 7.5% protein compared with rats fed 15 and 45% protein, whereas the activity of glutathione reductase was higher in rats fed 4 and 7.5% protein then in rats fed 15 or 45% protein. Dietary sulfur amino acids alone could account for the increase in glutathione concentration resulting from the increase in dietary protein from 7.5 to 15%. The limited availability of glutathione in animals fed the low protein diets could reduce the potential for detoxification of xenobiotics.
Sensitivity and adrenoceptor affinity in the mesenteric artery of the deoxycorticosterone acetate hypertensive rat
Authors: Perry Patsy A. , Webb R. Clinton
Published: April 2011

This study examines vascular reactivity to α-adrenoceptor agonists in mineralocorticoid (deoxycorticosterone acetate (DOCA–salt) hypertensive and normotensive rats. The rats were anesthetized and the mesenteric artery was excised and cut helically into strips that were mounted in a muscle bath for the measurement of isometric force development. Addition of norepinephrine, epinephrine, phenylephrine, methoxamine, or clonidine to the bath caused contractions in all arteries. Arteries from hypertensive rats were more sensitive (lower ED50 values) to each of the agonists than arteries from normotensive rats. α-Adrenoceptor affinity for phentolamine (Schild analysis; norepinephrine as the agonist) in hypertensive arteries was not significantly different from that in normotensive arteries. Maximal force generation to clonidine was greater in hypertensive arteries than in normotensive arteries. These results demonstrate an augmented vascular sensitivity to several α-adrenoceptor agonists in DOCA hypertensive rats. This change in sensitivity is independent of a change in affinity for the adrenoceptor antagonist, phentolamine. It may be that a change in receptor number or an alteration in a post-receptor activation event accounts for this enhanced adrenoceptor responsiveness in mineralocorticoid hypertension.
Expression of transforming growth factor alpha during development
Authors: Han V. K. M. , D'Ercole A. J. , Lee D. C.
Published: April 2011

Transforming growth factors (TGFs) are polypeptides that are produced by transformed and tumour cells, and that can confer phenotypic properties associated with transformation on normal cells in culture. One of these growth-regulating molecules, transforming growth factor alpha (TGF-α), is a 50 amino acid polypeptide that is related to epidermal growth factor (EGF) and binds to the EGF receptor. Previous studies have shown that TGF-α is expressed during rodent embryogenesis between 7 and 14 days gestation. To investigate the cellular sites of TGF-α mRNA expression during development, we have performed Northern analyses and in situ hybridization histochemistry on the conceptus and maternal tissues at various gestational ages. Contrary to previous reports, both Northern analyses and in situ hybridization histochemistry indicate that TGF-α mRNA is predominantly expressed in the maternal decidua and not in the embryo. Decidual expression is induced following implantation, peaks at day 8, and declines through day 15 when the decidua is being resorbed. In situ hybridization revealed that expression of TGF-α mRNA is highest in the region of decidua adjacent to the embryo and is low or nondetectable in the uterus, placenta, and embryo. In addition, we could not detect TGF-α mRNA expression in other maternal tissues, indicating that the induction of TGF-α transcripts in the decidua is tissue specific, and not a pleiotropic response to changes in hormonal milieu that occur during pregnancy. The developmentally regulated expression of TGF-α mRNA in the decidua, together with the presence of EGF receptors in this tissue, suggests that this peptide may stimulate mitosis and angiogenesis locally by an autocrine mechanism. Because EGF receptors are also present in the embryo and placenta, TGF-α may act on these tissues by a paracrine or endocrine mechanism.
Release of growth hormone from purified somatotrophs: effects of the calcium channel antagonists diltiazem and nifedipine on release induced by growth hormone-releasing factor
Authors: Lussier B. T. , Moor B. C. , French M. B. , Kraicer J.
Published: April 2011

We examined the effect of the voltage-sensitive Ca2+ channel antagonists, diltiazem and nifedipine, on basal and stimulated growth hormone (GH) release from purified somatotrophs. Our aim was to ascertain whether an influx of Ca2+ from the extracellular to the intracellular compartment is essential for augmented release. Basal release was decreased in a concentration-dependent manner by both diltiazem and nifedipine, while cAMP accumulation was unaffected. The release of GH induced by 29 mM K+ was blocked by diltiazem and nifedipine, at 10−7and 10−8 M, respectively. Again cAMP was unaffected. The release of GH induced by growth hormone-releasing factor was significantly reduced by 10−4 M diltiazem and completely blocked by nifedipine at a concentration of 10−6 M or greater. Where the antagonists were effective, the growth hormone-releasing factor induced increase in cAMP accumulation was augmented. We conclude that an influx of Ca2+ from the extracellular compartment is essential for stimulated GH release.
Morphine can stimulate prolactin release independent of a dopaminergic mechanism
Authors: Shin S. H. , Obonsawin M. C. , Vugt D. A. Van , Baby N. , Jhamandas K.
Published: April 2011

Prolactin release is controlled by prolactin-release inhibiting factor (PIF), possibly dopamine, and an unidentified putative hypothalamic prolactin-releasing factor (PRF). Morphine and related opioids may indirectly stimulate prolactin release by inhibiting PIF release and (or) by stimulating putative PRF release. In the present study, we have completely blocked the dopaminergic receptors in normal male rats by pretreatment with a large dose of pimozide (3 mg/kg) to demonstrate if putative PRF has a role in morphine-induced prolactin release. Morphine sulfate (10 mg/kg) was still able to stimulate prolactin release in the rat without any functional dopaminergic PIF receptors. When naloxone (3 mg/kg) was injected 20 min before the morphine in the pimozide-treated rat, plasma prolactin concentration was not affected by morphine indicating that the stimulatory effect of this opioid on prolactin release in the pimozide-pretreated rat was mediated by μ-receptors. We can conclude that morphine can stimulate prolactin release through a mechanism apparently independent of dopaminergic receptors, one possible route being through a putative PRF.
Effect of prolactin and cyclic AMP on 125I-labelled low density lipoprotein uptake and metabolism by luteinized porcine granulosa cells in culture
Authors: Rajkumar Kadaba , Ly Hoa , Chedrese Pedro J. , Murphy Bruce D.
Published: April 2011

The present study examines the effect of prolactin (PRL) and N6-21-O-dibutyryladenosine 3′5′-cyclic monophosphate (cAMP) on low density lipoprotein (LDL) uptake and metabolism by luteinized porcine granulosa cells in culture. Granulosa cells from preovulatory follicles were plated with 1% serum and 1 μg/mL of insulin for the first 48 h. Following plating (day 3) the cells were cultured in serum-free media with the same dose of insulin. The next day the medium was replaced with serum- and insulin-free medium, and to some cultures 1.23 IU/mL of human chorionic gonadotropin (hCG) was added. On day 5 the medium was again replaced and graded amounts of PRL (0, 0.03, 0.3, and 3 μg/mL) were added. Following 48 h of incubation with PRL, 20 μg/mL of 125I-labelled LDL was added to cultures. Surface-bound, internalized, and degraded LDLs were quantitated at 12 h following addition of LDL. To examine the effect of cAMP on LDL metabolism, the cells were exposed for 24 h to cAMP (3 mM) on day 6 of culture. PRL had a stimulatory effect on LDL degradation by luteinized granulosa cells. Pre-exposure of cells to hCG augmented the stimulatory effect of PRL. Addition of cAMP also enhanced LDL degradation by luteinized granulosa cells. Both PRL and cAMP increased surface binding of LDL in cells pre-exposed to hCG, but there was no effect on internalization. The increase in cell surface binding of LDL with PRL and cAMP was less than their effect on LDL degradation. It is concluded that PRL and cAMP enhance LDL metabolism in luteinized porcine granulosa cells by increasing surface binding of LDL and by a post-receptor mechanism. PRL may play a role in the supply of LDL-carried cholesterol for steroidogenesis by luteinized granulosa cells.
The effect of a weight-reducing diet on the nitrogen metabolism of obese adolescents
Authors: Pencharz P. B. , Clarke R. , Archibald E. H. , Vaisman N.
Published: April 2011

Rates of whole body amino nitrogen flux were measured in 16 obese adolescents undergoing weight reduction with a high protein low energy diet. The subjects received approximately 2.5 g of animal protein per day per kilogram ideal body weight and maintained nitrogen balance throughout the 18 days on the diet. Flux rates were calculated separately from the cumulative excretion of 15N in urinary ammonia and urea following the administration of a single dose of [15N]glycine. The pattern of 15N label appearance in urinary ammonia and urea nitrogen was followed for 72 h after the administration of [15N]glycine. Significant amounts of label continued to be excreted in both urinary ammonia and nitrogen for 36–48 h after label administration. The weight-reducing diet accelerated 15N cumulative excretion in urinary urea, but not in ammonia nitrogen compared with the control diet. Whole body nitrogen flux rates increased rapidly and significantly on the diet. Using the urea end product, this increase was evident on the 4th diet day, but not by the 7th or subsequent days. On the other hand, using the ammonia end product, flux rate increased markedly (p < 0.0001) and remained elevated throughout the whole study. Our results demonstrate adaptive changes in whole body amino-nitrogen metabolism in response to the reducing diet. Different patterns of change are seen depending upon whether an ammonia or a urea end product is used. Our data thus add to the evidence for compartmentation of the body's amino-nitrogen pools.
A reappraisal of protein turnover values in neonates fed human milk or formula
Authors: Pencharz P. B. , Clarke R. , Papageorgiou A. , Farri L.
Published: April 2011

We investigated the effect of human milk feeding on the nitrogen metabolism of appropriate-for-gestational age infants of birth weight 1.5–2.0 kg. Eight infants received pooled mature human milk. The remaining 20 were divided into two equal groups, who received one of two low-protein, milk-based formulae. The formulae were identical in composition except for the protein source, which was either casein- or whey-predominant. The three diet groups received similar total nitrogen (390 mg N∙kg−1∙d−1) and energy (500 kJ∙kg−1∙d−1) intakes. The human-milk-fed group, however, received a significantly higher intake of nonprotein and urea nitrogen and a significantly lower true protein nitrogen. Nitrogen metabolism was studied using a modified constant infusion of [15N]glycine, mixed with the feeding every 2–3 h. Urine was collected in approximately 3-h aliquots and analysed for total ammonia and urea nitrogen. Excretion of the 15N label was measured in urinary urea and ammonia. No differences were seen between the three diet groups in total [15N]urea or [15N]ammonia urinary excretion. However, the concentration of 15N in urinary urea in the human-milk-fed group was lower than in the two formula-fed groups. This reduction in concentration appeared due to a higher dietary intake of urea among the human-milk-fed group, and the consequent dilution of the label in the urine. As a result, protein turnover rates calculated from the [15N]urea end product were artificially raised in the milk-fed group, and were significantly higher than those in the formula groups. No differences were noted between the three diet groups in nitrogen turnover rates derived from the ammonia label. These rates averaged 61% of those derived from the urea end product. The two nitrogenous end products (ammonia and urea) appear to reflect different aspects of the neonates' nitrogen metabolism, in the form of pools or compartments that may be interchanging but are not always equilibrated.Key words: human milk, premature infant, low birth weight, nitrogen isotopes, protein metabolism.
Characterization of ion movements and their relationship to muscarinic receptor binding and excitation–contraction coupling in guinea pig ileal longitudinal smooth muscle
Authors: Bolger G. T. , Luchowski E. M. , Triggle D. J.
Published: April 2011

The relationship between ion movements (sodium uptake and potassium release) and agonist-induced contractile responses or muscarinic receptor binding was investigated in the guinea pig ileal longitudinal muscle (GPLM). Sodium uptake and potassium release were agonist-dependent, concentration-dependent, and stereoselective, with the following rank order of maximum ion movement: muscarinic agonists > histamine > substance P = serotonin. Potassium depolarization did not initiate sodium uptake or potassium release. Sodium uptake was rapid and monophasic, preceding potassium release which was biphasic in nature. Full muscarinic agonists produced equal maximal increases in sodium uptake, while maximal potassium release varied for all muscarinic agonists and in addition differed from sodium uptake in the following ways: time course, stereoselectivity, sensitivity to calcium antagonists, modulation by the guanylyl nucleotide derivative, 5′-guanylylimidodiphosphate (Gpp(NH)p), and inhibition by muscarinic receptor blockade with benzilylcholine mustard. The calcium ionophores A23187 and ionomycin (SQ23377) did not produce any sodium uptake; A23187 but not ionomycin produced potassium release comparable to that evoked by muscarinic agonists. Ion movement in response to combinations of agonists were not additive. Muscarinic agonist binding as measured by competition for [3H]quinuclidinyl benzilate ([3H]QNB) binding, was best described by multiple sites and was regulated by Gpp(NH)p. Excellent correlations were observed between the dissociation constants for binding and sodium uptake, potassium release, and contraction. The best correlations were those between the pharmacologic responses and the high affinity binding site in the absence, and the low affinity site in the presence, of Gpp(NH)p, respectively. Furthermore, the potencies of muscarinic agonists to evoke ion movements and to inhibit [3H]QNB binding were similar, and from one to two orders of magnitude less than those for contraction. It is suggested that contraction and potassium release were mediated by the high affinity, and sodium uptake by the low and average affinity muscarinic agonist binding sites, respectively. These findings suggest an agonist-activated receptor–effector coupling model in GPLM that leads to the activation of sodium uptake, potassium release, and subsequently, contraction.Key words: smooth muscle, contraction, muscarinic receptors, ion movements, excitation–contraction coupling.
The effects of midazolam on hippocampal dentate gyrus granule neurons from young and old Fischer 344 rats
Authors: Reynolds J. N. , Carlen P. L.
Published: April 2011

The effects of midazolam (3 nM) perfusion on the membrane and synaptic properties of dentate gyrus granule neurons were examined in hippocampal slices obtained from young adult (4–6 months) and old (24–26 months) Fischer 344 rats. In young neurons, midazolam perfusion resulted in a hyperpolarization of the resting membrane potential with no apparent change in the input resistance. Midazolam perfusion also produced a significant increase in the amplitude of the post-spike train afterhyperpolarization (AHP). In neurons obtained from old animals, midazolam perfusion also produced a hyperpolarization of the resting membrane potential but did not signficantly change the AHP. These effects may result from altered calcium homeostasis in neurons of the aged brain, and suggest that at least some of the direct actions of benzodiazepines on mammalian central neurons are altered during aging.Key words: aging, midazolam, hippocampus, dentate granule neuron, post-spike train afterhyperpolarization.
Energy balance and diabetes. The effects of cold exposure, exercise training, and diet composition on glucose tolerance and glucose metabolism in rat peripheral tissues
Authors: Bukowiecki Ludwik Jan
Published: April 2011

The effects of cold exposure, exercise training, and diet (high fat versus high carbohydrate) on glucose tolerance and glucose metabolism in rat peripheral tissues will be briefly reviewed. Stimulation of energy expenditure by cold exposure (4 °C) or exercise training generally leads to decreased plasma insulin levels and to an improvement in glucose tolerance, suggesting that insulin action on peripheral tissues is increased when energy expenditure is stimulated. On the contrary, feeding high-fat diets to sedentary rats living in the warm (25 °C) induces hyperinsulinemia and insulin resistance resulting in a marked deterioration of glucose tolerance. Nevertheless, cold exposure reverses the diabetogenic effects of high-fat feeding, demonstrating that nutrition-induced insulin resistance is amplified in sedentary animals living at temperatures close to thermoneutrality. Radioactive tracer studies of 2-deoxyglucose uptake in peripheral tissues revealed that cold exposure synergistically potentiates the effects of insulin on glucose uptake in skeletal muscles as well as in white and brown adipose tissues. However, more recent data showed that cold exposure improves glucose tolerance and stimulates glucose uptake in starved animals (ie., in the virtual absence of circulating insulin) nearly by the same order of magnitude as in fed animals. It is therefore concluded that cold exposure, and possibly also exercise, improve glucose tolerance and stimulate glucose uptake in peripheral tissues primarily by enhancing glucose oxidation via insulin-independent pathways, and secondarily by increasing the responsiveness of peripheral tissues to insulin.Key words: insulin, brown adipose tissue, skeletal muscle, 2-deoxyglucose, diabetes.
Role of thermogenesis in the regulation of energy balance in relation to obesity
Authors: Himms-Hagen Jean
Published: April 2011

Obligatory thermogenesis is a necessary accompaniment of all metabolic processes involved in maintenance of the body in the living state, and occurs in ail organs. It includes energy expenditure involved in ingesting, digesting, and processing food (thermic effect of food (TEF)). At certain life stages extra energy expenditure for growth, pregnancy, or lactation would also be obligatory. Facultative thermogenesis is superimposed on obligatory thermogenesis and can be rapidly switched on and rapidly suppressed by the nervous system. Facultative thermogenesis is important in both thermal balance, in which control of thermoregulatory thermogenesis (shivering in muscle, nonshivering in brown adipose tissue (BAT)) balances neural control of heat loss mechanisms, and in energy balance, in which control of facultative thermogenesis (exercise-induced in muscle, diet-induced thermogenesis (DIT) in BAT) balances control of energy intake. Thermal balance (i.e., body temperature) is much more stringently controlled than energy balance (i.e., body energy stores). Reduced energy expenditure for thermogenesis is important in two types of obesity in laboratory animals. In the first type, deficient DIT in BAT is a prominent feature of altered energy balance. It may or may not be associated with hyperphagia. In a second type, reduced cold-induced thermogenesis in BAT as well as in other organs is a prominent feature of altered thermal balance. This in turn results in altered energy balance and obesity, exacerbated in some examples by hyperphagia. In some of the hyperphagic obese animals it is likely that the exaggerated obligatory thermic effect of food so alters thermal balance that BAT thermogenesis is suppressed. In all obese animals, deficient hypothalamic control of facultative thermogenesis and (or) food intake is implicated.Key words: thermogenesis, brown adipose tissue, energy balance, obesity, cold, thermoregulation, diet.
Effects of verapamil on sympathetic tone in normal and chronic sinoaortic-denervated conscious dogs
Authors: Damase-Michel Christine , Tran Marie-Antoinette , Montastruc Jean-Louis
Published: April 2011

Previous studies have shown that calcium channel blockers from the dihydropyridine group (such as nicardipine) induce an increase in sympathetic tone from a central origin in chronic sinoaortic-denervated (SAD) dogs. In the present study, we investigated to see if verapamil possesses such properties. The effects of acute injection of verapamil (0.2 mg/kg i.v.) were compared in normal and SAD conscious dogs. Verapamil induced a decrease in blood pressure in the two groups of animals, and an increase in heart rate and plasma catecholamines (noradrenaline and adrenaline) in normal but not in SAD dogs. Contrary to the dihydropyridine studies (nicardipine), we did not find any evidence for a centrally mediated sympathoexcitatory effect of verapamil in conscious SAD dogs.Key words: verapamil, plasma catecholamines, hypertension, sinoaortic denervation.
Altered peripheral noradrenergic activity in intact and sinoaortic denervated Dahl rats
Authors: Peuler J. D. , Patel K. P. , Morgan D. A. , Whiteis C. A. , Lund D. D. , Pardini B. J. , Schmid P. G.
Published: April 2011

Development of salt-induced hypertension in Dahl salt-sensitive (S) rats is dependent on sympathetic overactivity which may be partially related to arterial baroreflex dysfunction and, therefore, is regionally selective. Our first experiment was designed to determine which regions have elevated sympathetic activity in Dahl S compared with Dahl salt-resistant (R) rats. Weanling (4-week-old) female Dahl R and S rats were fed low or high salt diets (0.13% and 8% NaCl) until 10 weeks of age. Norepinephrine (NE) synthesis was blocked with α-methyl-p-tyrosine, and the fractional decline of NE concentration was measured in various tissues. Dahl S rats with increases in both arterial pressure and left ventricular weight demonstrated increased NE turnover in the sinoatrial node, the atrial appendages, the cardiac ventricles, and the renal cortex. In all of these tissues except the cardiac ventricle, increases were associated with high salt intake. Our second experiment was designed to test if arterial baroreflex dysfunction could account for regional increases in sympathetic activity. Separate groups of Dahl R and S rats fed high salt were subjected to either sham surgery or sinoaortic baroreceptor denervation 1 week prior to turnover determinations. Sinoaortic baroreceptor denervation abolished differences in NE turnover between salt-fed Dahl R and S rats in the cardiac sinoatrial node and the atrial appendages, but not in the cardiac ventricles and the renal cortex. Sinoaortic baroreceptor denervation also abolished differences between salt-fed Dahl S and R rats in the spleen but not the duodenum. Thus in awake, undisturbed Dahl S rats, sympathetic activity may be increased in the cardiac ventricles, regardless of salt intake. High salt intake may induce elevated sympathetic activity in the renal cortex and in the cardiac atria and sinoatrial node of Dahl S but not R rats. Sinoaortic baroreflex dysfunction in Dahl S rats may contribute to some, but not all, regional increases in sympathetic activity.Key words: high salt intake, hypertension, cardiac hypertrophy, norepinephrine turnover, sympathetic activity, sinoaortic denervation.
Intestinal motility during acute Yersinia enterocolitica enteritis in rabbits
Authors: Scott R. B. , Gall D. G. , Diamant S. C.
Published: April 2011

To determine if Yersinia enterocolitica (YE) enteritis is associated with an alteration of intestinal myoelectric and motor activity, and with an increased rate of aboral transit, New Zealand white rabbits (500–900 g) were surgically prepared with ileal bipolar electrodes and a manometry catheter adjacent to the distal electrode. One week later animals were inoculated with 1010 organisms of YE in 10 mL NaHCO3 (infected group) or 10 mL NaHCO3 (sham-infected pair-fed and control groups). Daily food intake, weight gain, YE excretion, and stool pattern were noted. Intestinal myoelectric and motor activity over a 6- to 8- h period before and 3, 6, and 14 days after inoculation was compared in infected (I), pair-fed (PF), and control (C) groups. Intestinal transit was evaluated in I and C animals on days 3 and 6 after inoculation by measuring the distribution in the intestinal lumen of 51Cr 20 min after it was instilled directly into the jejunum. Infected animals exhibited diarrhea, fecal excretion of YE, and significantly decreased food intake, weight gain, and survival (11.4 ± 0.6 days). Infection was associated with a significant (p < 0.05) decrease in both the cycle period of the migrating myoelectric complex (MMC) and the total number of single, paired, and (or) clustered contractions per MMC, and a significant (p < 0.001) increase in duration of phase III of the MMC. There was no change in intestinal slow wave frequency (19 cycles/min), motility index per MMC, or the percentage of contractions that propagated in an orad (7%) or aboral (69%) direction or that appeared stationary (25%). The changes in myoelectric and motor activity were specific for YE infection (not related to decreased food intake and weight gain) and were associated with a significantly increased rate of aboral transit. Thus, the inflammatory enteritis induced by YE is associated with alterations of intestinal myoelectric and motor activity, and an increased rate of aboral transit.Key words: Yersinia enterocolitica, infection, intestine, motility, transit.
Ah receptor in spleen of rodent and primate species: detection by binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin
Authors: Roberts Eve A. , Vella Lynn M. , Golas Cheryl L. , Dafoe Leslie A. , Okey Allan B.
Published: April 2011

In many species systemic toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is manifested by a generalized wasting syndrome accompanied by a variety of specific organ changes including atrophy of the thymus and spleen. TCDD toxicity in most tissues is thought to be mediated by the Ah receptor. Although the spleen is a prime target for TCDD toxicity, the possible presence of Ah receptor in the spleen has not previously been investigated. Specific binding of [3H]TCDD to Ah receptor in spleen cytosols was assessed by velocity sedimentation on sucrose gradients. Ah receptor was detected in spleen cytosols from adult Rhesus monkeys (mean ± SEM, 36 ± 8 fmol/mg cytosol protein), fetal Rhesus monkeys (9 ± 6), Sprague–Dawley rats (20 ± 5), C57BL/6J mice (18 ± 2), New Zealand white rabbits (19 ± 2), and Hartley guinea pigs (15 ± 2). Ah receptor was not detectable in spleen cytosol from genetically "nonresponsive" DBA/2J mice or from Golden Syrian hamsters, a species resistant to toxicity of TCDD. Molecular properties of Ah receptor from spleen were similar to those of the receptor from liver of the same species. The high Ah receptor content in spleen cytosols from those species that are most susceptible to TCDD toxicity is consistent with the view that the Ah receptor mediates TCDD toxicity in spleen as well as in other tissues.Key words: Ah receptor, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, immunotoxicity, spleen.