bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of high affinity nitrobenzylthioinosine binding sites in mammalian cortical membranes: multiple forms of central nervous system nucleoside transporters?
Authors: Hammond James R. , Clanachan Alexander S.
Published: April 2011

Specific binding of [3H]nitrobenzylthioinosine to cortical membranes from several mammalian species was investigated. Rat, mouse, guinea pig, and dog membranes contained an apparent single class of binding sites; there was, however, a marked species-dependent variation in their affinity for [3H]nitrobenzylthioinosine. Rabbit cortical membranes contained two classes of binding sites and the high and low affinity components were similar to those found in guinea pig and dog cortical membranes, respectively. The [3H]nkrobenzylthioinosine binding sites in rat and the low affinity sites in rabbit were atypical in that they exhibited a low affinity for dipyridamole. It is proposed that these latter sites may represent a form of the central nervous system nucleoside transport system which is less susceptible to inhibition by dipyridamole.
Progesterone derivatives that bind to the digitalis receptor: effects on 86Rb uptake and contractility in the isolated guinea pig heart
Authors: LaBella Frank S. , Bihler Ivan , Kim Ryung-Soon
Published: April 2011

Chlormadinone acetate, 6-chloro-4,6-pregnadien-17α-ol-3,20-dione 17-acetate (CMA), a progestin that binds to the cardiac glycoside (CG) receptor, inhibits 86Rb uptake in slices of the guinea pig heart (Langendorff preparation), previously perfused with the steroid in Krebs – Henseleit – bicarbonate with or without 0.125% serum albumin. CMA consistently inhibits 86Rb uptake at low concentrations, < 10−8 M, is more potent than ouabain in this regard, and at these concentrations usually does not affect contractility, although occasional instances of transient positive inotropy occur. At higher concentrations, (10−7 and 10−6 M) uptake of 86Rb by CMA is depressed further and is usually accompanied by diminished contractile force. CMA was reduced to the 3β-hydroxy derivative and converted to the more water-soluble 3β-hemisuccinate (CMA-S). Occasional positive, although transient, increases in contractile force were elicited by CMA-S, but cardiac depression predominated, and higher concentrations induced cardiotoxicity. The addition of 10−7 to 10−6 M CMA-S to perfusion medium containing a cardiostimulant concentration (10−6 M) of ouabagenin resulted in depression of contractility. We propose several alternative hypotheses to explain our results: (a) CMA and CG compete for the same receptor site (Na+–K+ ATPase) and both drugs inhibit the enzyme; only the CG-induced conformation of the receptor is coupled to the mechanism responsible for positive inotropy; (b) CMA and CG compete for sites coupled to both pump inhibition and positive inotropy, but CMA, additionally, has effects on the cardiac cell that antagonize positive inotropy; the often described depressant action of progesterone on cardiac tissue may reside, as well, in CMA and might counteract to a variable extent any inherent positive inotropic action; (c) both CMA and CG inhibit the pump; only CG interacts with an additional site linked to positive inotropy and this action is antagonized by CMA; and (d) occasional transient increases but more frequent depression in contractile force elicited by the progesterone derivatives, the depression of contractility by low concentrations of CG, and the apparent pump stimulation by low concentrations of both classes of compounds reflect the differing affinities of CMA, CMA-S, and individual CGs for receptor sites mediating pump inhibition, positive inotropy, and negative inotropy.
Amino acid and dipeptide absorption in rats fed chemically defined diets of differing fiber composition
Authors: Freeman Hugh James
Published: April 2011

In rats chronically fed a fiber-free diet or one of the three nutritionally equivalent fiber-containing diets, in vivo jejunal absorption of L-leucine from a free amino acid mixture of L-leucine and glycine as well as equimolar solutions of the dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. In addition, total and brush border amino peptidase activities for the two dipeptide substrates were examined in small bowel segments. With two of three fiber diet groups, absorption of L-leucine from the free amino acid solution was reduced without a detectable change in peptide transport or aminopeptidase activities. This investigation provides evidence that peptide transport mechanisms are relatively spared with long-term feeding of fiber-containing diets similar to observations recorded in disease states associated with protein-energy malnutrition.
Intestinal absorption of free oleic acid in the unanesthetized rat: evidence for a saturable component?
Authors: Hollander Daniel , Chow San Laung , Dadufalza Violetta D.
Published: April 2011

The intestinal absorption of free oleic acid at low intraluminal concentrations and the influence of luminal factors on its absorption were studied in the unanesthetized rat. The relationship between oleic acid concentration (30–2500 μM) and its rate of absorptions fitted best to a rectangular hyperbola (y = x/(2.19 + 0.0015x), r = 0.94). Oleic acid's rate of absorption increased as the hydrogen ion and sodium taurocholate concentrations were increased or as the thickness and resistance of the unstirred water layer were diminished or following the addition of lysolecithin. The additions of the artificial detergent Tween-80, or lecithin and linoleic, linolenic and arachidonic acids to the perfusate decreased oleic acid's rate of absorption. It was concluded that oleic acid absorption in this range of concentrations displays apparent saturation kinetics which are due to unstirred layer effects, limited aqueous solubility of oleic acid and possible saturation of cytosol fatty acid binding proteins. Factors which increase oleic acid's protonated concentration or diminish the unstirred layer resistance, enhance its absorption rate, while factors which enhance its micellar solubility or interfere with its transfer out of the cell membrane decrease its overall rate of absorption.
Antagonism by the tetramine disulfide benextramine of the inhibitory effects mediated by prejunctional alpha2-adrenoceptors and by postjunctional histamine H2 receptors in the mouse vas deferens
Authors: Vohra M. M. , Chaudhry A.
Published: April 2011

The actions of benextramine, which blocks postjunctional alpha-adrenoceptors noncompetitively and irreversibly (non-equilibrium type) on prejunctional alpha-adrenoceptors (alpha2) and postjunctional histamine H2 receptors, were studied in the mouse vas deferens, using clonidine and histamine, respectively, as the agonists. Both agonists caused a dose-related inhibition of the electrically evoked twitch responses, an inhibition that their respective antagonists (yohimbine or phentolamine, and cimetidine) antagonized competitively. Benextramine, however, antagonized the agonists' inhibitory effect noncompetitively. At the concentrations used, while clonidine or yohimbine and phentolamine protected the prejunctional alpha-adrenoceptors (alpha2) against the benextramine noncompetitive blockade, histamine or cimetidine failed to protect the histamine H2 receptor against benextramine blockade. Therefore, although benextramine acts prejunctionally to block the alpha2-adrenoceptors in the mouse vas deferens either by interacting directly with the same site as clonidine or yohimbine and phentolamine, or allosterically with a site close to it, it does not appear to act irreversibly, either directly or allosterically, with the same site as histamine or cimetidine. The mechanism by which benextramine blocks the histamine-induced inhibition of the electrically evoked twitch response in the mouse vas deferens remains to be established.
Modulation of myosin isoenzyme populations and activities of monoamine oxidase and phenylethanolamine-N-methyltransferase in pressure loaded and normal rat heart by swimming exercise and stress arising from electrostimulation in pairs
Authors: Rupp Heinz , Felbier Hans-Richard , Bukhari Abid R. , Jacob Ruthard
Published: April 2011

The question of whether the effects of physical exercise on the heart of 15-weeks normotensive and hypertensive rats can be modulated by additional stressors was studied. Intermittent swimming (33–35 °C water, maximum 2 × 1.5 h/day, 2–6 weeks) was employed as a model of exercise. Electrostimulation of rats in pairs (maximum 2 × 1.5 h/day, 6 weeks) served as a model leading predominantly to stress. When the above procedures were combined, electrostimulation in pairs was performed in one session and was followed up by swimming. The myosin isoenzyme population was used as a marker of changes in contractile performance of myofibrils. Activities of the catecholamine-degrading enzyme monoamine oxidase (MAO) and the adrenaline-synthesizing enzyme phenylethanolamine-N-methyl transferase (PNMT) served to monitor chronic alterations of catecholamine turnover in myocardium. Redistribution in favour of VM-1 (ventricular myosin isoenzyme 1) occurred as early as 2 weeks after the onset of intermittent swimming and was observed under several experimental conditions. The redirection of genetic expression of the isoenzymes was not linked to the presence of an increased ratio of right to left ventricular weight, most probably arising from intermittent hypoxia during drownproofing. The myosin isoenzyme population of swimming spontaneously hypertensive rats (SHR) resembled that of sedentary Wistar rats. The enzyme activities of MAO and PNMT were both significantly reduced following 6 weeks intermittent swimming in Wistar rats and SHR. This can most probably be attributed to the exercise component of swimming which, on average, led to reduced catecholamine turnover in heart. Electrostimulation of rats in pairs for 6 weeks, which resulted in aggressivity and aggressions, did not alter the myosin isoenzyme population in Wistar rats; in SHR, it further augmented the proportion of VM-3 (ventricular myosin isoenzyme 3), which had already increased in the sedentary state. Furthermore, electrostimulation increased PNMT activity, but did not affect MAO activity. Electrostimulation in pairs, followed by swimming, altered the myosin isoenzyme population in the same way as did swimming alone. However, the activities of PNMT and MAO seemed to be governed by the routine involving stress and not by the exercise routine. This demonstrates that stressors supplementing exercise can decisively modify or even prevent reactions of the organism in response to exercise. With regards to the functional consequences for contractile performance, it can be concluded that swimming exercise applied in addition to stressors can induce transformation of myocardium towards a fast-type muscle which would appear to be better adapted for such demands as high heart rate encountered during stress.
Effect of whole and fractionated dietary alfalfa meal on zearalenone toxicosis and metabolism in rats and swine
Authors: Stangroom K. E. , Smith T. K.
Published: April 2011

Experiments were conducted to determine the mechanism by which dietary alfalfa can protect against zearalenone toxicosis. Female weanling rats were fed semipurified diets containing whole alfalfa meal, fractionated alfalfa meal (fiber, solvent extract, and water extract), and purified components of alfalfa (coumestrol, saponin, lignin, coumestrol + lignin, and saponin + lignin) with and without 250 mg zearalenone/kg of diet. All ingredients were provided for 2 weeks at levels corresponding to those found in diets containing 15 and 25% alfalfa. Yorkshire gilts were fed 15 and 25% alfalfa meal with and without 10 mg zearalenone/kg of diet for 4 weeks. The feeding of zearalenone to rats reduced growth and food consumption but this was overcome by 25% alfalfa. Zearalenone also increased the activity of hepatic 3α-hydroxysteroid dehydrogenase (3α-HSD), the enzyme believed to metabolize zearalenone to α- and β-zearalenols. Dietary alfalfa did not overcome this effect. Alfalfa fiber was the only fraction to partially overcome the growth-depressing effects of zearalenone while the other fractions had no beneficial effects and 3α-HSD was not affected by diet. None of the purified components affected growth parameters or 3α-HSD. The enzyme was also not affected by zearalenone or alfalfa in swine diets. Coumestrol, α-zearalenone, and β-zearalenone were shown to be competitive inhibitors of 3α-HSD in rat liver. It was concluded that the fiber fraction of alfalfa protects against zearalenone toxicity, and that this effect is not dependent on coumestrol or saponin and is not likely mediated through 3α-HSD.
Dynamic changes in plasma luteinizing hormone and testosterone after stress in the male rat. Influence of adrenalectomy
Authors: Lescoat Gérard , Lescoat Denise , Garnier Danièle
Published: April 2011

In 60-day old intact male rats, stress imposed by a strange environment increased the levels of plasma LH and testosterone. Adrenalectomy, performed at 50 days of age, decreased plasma level of testosterone in basal conditions. However, without affecting the plasma level of LH significantly, stress increased plasma testosterone, albeit to a lesser extent, in the adrenalectomized rats. Stimulation of the testicular secretion by the high level of ACTH seems to be the most likely explanation for the observed testosterone peak in the adrenalectomized rat.
The effects of cholecystokinin-octapeptide and pentagastrin on electrical and motor activities of canine colonic circular muscle
Authors: Huizinga Jan D. , Chang Gordon , Diamant Nicholas E. , El-Sharkawy Taher Y.
Published: April 2011

The effects of cholecystokinin-octapeptide (CCK-OP) and pentagastrin on electrical and motor activities of circular muscle of the canine colon were studied with the sucrose gap technique. Additional organ bath experiments were performed to further characterize the motor response to the peptides and to elucidate their site of action. The electrical activity consisted of slow waves having an initial potential followed by a plateau potential, at a regular frequency of 4.5 cycles/min. Both peptides prolonged the duration and increased the amplitude of the plateau phase of the slow waves. Concomitantly, the slow wave frequency was reduced. In addition, CCK-OP increased spiking activity. Both spiking activity and the prolonged plateau potential generated contractile activity, prolonged phasic contraction occurring with slow waves with a prolonged plateau. In organ bath experiments, both CCK-OP and pentagastrin increased the basal tone of the muscle strips and prolonged the duration of the phasic contractions. The prolongation of the duration of the contractions was not antagonized by tetrodotoxin (TTX) and atropine. CCK-OP but not pentagastrin increased the force of contractions, this action was not affected by atropine but was reduced in the presence of TTX, suggesting that the increase in force may be partially mediated by noncholinergic excitatory nerves. The increase in basal tension by the peptides was enhanced in the presence of TTX indicating that myenteric inhibitory neurones were tonically active under our experimental conditions. The results provide the electrophysiological basis for CCK-OP and pentagastrin induced changes in colonic motility.
Effects of exercise on insulin binding and glucose metabolism in muscle
Authors: Bonen A. , Tan M. H. , Watson-Wright W. M.
Published: April 2011

To elucidate the mechanism of enhanced insulin sensitivity by muscle after exercise, we studied insulin binding, 2-deoxy-D-[1-14C]glucose (2-DOG) uptake and [5-3H]glucose utilization in glycolysis and glycogenesis in soleus and extensor digitorum longus (EDL) muscles of mice after 60 min of treadmill exercise. In the soleus, glycogenesis was increased after exercise (P < 0.05) and remained sensitive to the action of insulin. Postexercise insulin-stimulated glycolysis was also increased in the soleus (P < 0.05). In the EDL, glycogenesis was increased after exercise (P < 0.05). However, this was already maximal in the absence of insulin and was not further stimulated by insulin (0.1–4 nM). The disposal of glucose occurred primarily via the glycolytic pathway (>60%) in the soleus and EDL at rest and after exercise. The uptake of 2-DOG uptake was not altered in the soleus after exercise (4 h incubation at 18 °C). However, with 1-h incubations at 37 °C, a marked increase in 2-DOG uptake after exercise was observed in the soleus (P < 0.05) in the absence (0 nM) and presence of insulin (0.2–4 nM) (P < 0.05). A similar postexercise increase in 2-DOG uptake occurred in EDL. Despite the marked increase in glucose uptake and metabolism, no changes in insulin binding were apparent in either EDL or soleus at 37 °C or 18 °C. This study shows that the postexercise increase of glucose disposal does not appear to be directly attributable to increments in insulin binding to slow-twitch and fast-twitch muscles. Also, after exercise the increments in glucose metabolism differ markedly in the two types of muscle.
Symposium Hypertensive mechanisms: The role of altered smooth muscle and membrane function in the etiology of hypertension
Authors: Triggle C. R.
Published: April 2011

The etiology of essential hypertension has been under intensive investigation for a number of years, and the availability of a number of rat models of this disease has aided our understanding of the relationship between abnormalities in cardiovascular regulatory function and hypertension. It is accepted that abnormalities at a number of levels of these regulatory processes could be the basis of the pathological process; however, the cause–effect relationship has not always been clearly established. This introduction addresses the potential relationship between a number of parameters and the control of blood pressure, and the Symposium attempts to relate altered smooth muscle and membrane function to hypertension.
The relationship between altered blood vessel structure, hypertension, and the sympathetic nervous system
Authors: Scott T. M. , Galway G.
Published: April 2011

The relationship between sympathetic innervation and arterial medial development has been examined in normotensive, hypertensive, and diabetic rats. Using the jejunal artery as a model, the number of nerve fibres innervating the artery as determined from fluorescent preparations, and the medial thickness and lumen diameter as measured from resin embedded specimens were correlated from animals prepared in various ways. The rats used were normal Sprague–Dawley (SD), SD with induced hypertension, SD with diabetes induced with streptozotocin, SD sympathectomized with 6-hydroxydopamine, spontaneously hypertensive rats (SHR), SHR treated with capsaicin to prevent hypertension development, Wistar Kyoto rats (WKY), and WKY treated with capsaicin. Examination of the jejunal arteries from these rats at 12 weeks of age following normal development, or 8 weeks of hypertension development, or 8 and 12 weeks of diabetes, showed that increased innervation occurred in the SHR under all conditions, and in the diabetic rats after 8 weeks of diabetes. Medial hypertrophy occurred in the SHR and in the SD hypertensive only. It is concluded that the special relationship which exists between the sympathetic innervation and arterial media in the SHR does not occur during hypertension development in the SD rat, nor is it necessary for normal medial development in the SD rat. The sympathetic innervation does appear to have a trophic influence on vascular smooth muscle of diabetic rats, at least in the early stages of the disease.
The effect of acid–base balance on fatigue of skeletal muscle
Authors: Mainwood G. W. , Renaud J. M.
Published: April 2011

H+ ions are generated rapidly when muscles are maximally activated. This results in an intracellular proton load. Typical proton loads in active muscles reach a level of 20–25 μmol∙g−1, resulting in a fall in intracellular pH of 0.3–0.5 units in mammalian muscle and 0.6–0.8 units in frog muscle. In isolated frog muscles stimulated to fatigue a proton load of this magnitude is developed, and at the same time maximum isometric force is suppressed by 70–80%. Proton loss is slowed when external pH is kept low. This is paralleled by a slow recovery of contractile tension and seems to support the idea that suppression results from intracellular acidosis. Nonfatigued muscles subjected to similar intracellular proton loads by high CO2 levels show a suppression of maximal tension by only about 30%. This indicates that only a part of the suppression during fatigue is normally due to the direct effect of intracellular acidosis. Further evidence for a component of fatigue that is not due to intracellular acidosis is provided by the fact that some muscle preparations (rat diaphragm) can be fatigued with very little lactate accumulation and very low proton loads. Even under these conditions, a low external pH (6.2) can slow recovery of tension development 10-fold compared with normal pH (7.4). We must conclude that there are at least two components to fatigue. One, due to a direct effect of intracellular acidosis, acting directly on the myofibrils, accounts for a part of the suppression of contractile force. A second, which in many cases may be the major component, is not dependent on intracellular acidosis. This component seems to be due to a change of state in one or more of the steps of the excitation–contraction coupling process. Reversal of this state is sensitive to external pH which suggests that this component is accessible from the outside of the cell.
Sugar uptake into a primary culture of dog kidney proximal tubular cells
Authors: Yau C. , Rao L. , Silverman M.
Published: April 2011

We describe the functional characteristics of a new primary culture system derived from a suspension of dog proximal tubular cells. The culture system is maintained on alpha minimal essential medium with 15% fetal calf serum supplementation. At confluency the cultured cells demonstrate the following: (i) typical epithelial morphology using light microscopy, with multiple dome formation inhibited by ouabain; (ii) strong binding with a polyclonal antibody directed against dog proximal tubular brush border membrane antigens; (iii) high concentration of alkaline phosphatase activity by histochemical staining; and (iv) 25-hydroxycholecalciferol (25(OH)D3)-24-hydroxylase activity. Sugar transport was assessed using α-methyl-D-glucopyranoside (αMG), a nonmetabolizable analog of D-glucose, as well as L-glucose, and 3-O-methyl-D-glucose (3OMG). The transport of αMG was stereospecific; temperature sensitive; inhibited strongly by phlorizin but not by cytochalasin B, phloretin, or 3OMG; and Na dependent. The transport of 3OMG is stereospecific, temperature sensitive, and inhibited strongly by phloretin and cytochalasin B, but not by phlorizin. Despite the apparent heterogeneity of cell type, this primary culture system exhibits many features of normal dog proximal tubule function.
Postabsorption antidotal effects of N-acetylcysteine on acetaminophen-induced hepatotoxicity in the mouse
Authors: Whitehouse L. W. , Wong L. T. , Paul C. J. , Pakuts A. , Solomonraj G.
Published: April 2011

Male Swiss Webster mice, treated with N-acetylcysteine (NAC, 500 mg/kg po) 1 h following acetaminophen (NAPA, 350 mg/kg po) administration, had control levels of transaminases indicating that NAC protects against NAPA-induced hepatotoxicity by postabsorption antidotal mechanism(s). Hepatic congestion induced by NAPA was reduced by NAC. Significantly higher elimination rate constants (K) for indocyanine green (500 μg/kg, iv) in mice treated with NAPA and NAC (K = 0.676 ± 0.062) than in animals receiving NAPA alone (0.341 ± 0.105) suggested NAC improved or preserved the hepatic circulation of the compromised liver. This NAC-induced improvement and (or) preservation of hepatic circulation was reflected in biliary and urinary excretion of acetaminophen and its metabolites by a general increase in elimination during the first 6 h (70.2 ± 2.6 vs. 32.6 ± 7.1%), and in the repletion of glutathione (GSH) in the liver by a return to control levels more quickly (3 vs. >5 h) following depletion by NAPA. The metabolic consequence of the postabsorption antidotal effect of NAC in the compromised liver was a preferential excretion of sulphydryl-derived metabolites in the 1–4 h bile (GSH conjugate 11.30 ± 1.25 vs. 7.25 ± 0.39%) which was subsequently observed in the urine by preferential excretion of glutathione degradation products.
Association of the positive inotropic action of ouabain with a second species of digitalis receptors
Authors: Kurobane Itsuo , Nandi Dhirendra L. , Okita George T.
Published: April 2011

Studies were conducted to determine whether Na–K ATPase or a second species of digitalis receptors in canine cardiac sarcolemma membrane preparations is associated with the positive inotropic action of nontoxic concentrations of ouabain. [3H]ouabain association and dissociation experiments using highly enriched sarcolemma preparations from canine ventricle indicate the presence of two species of ouabain binding receptors. Ouabain binding to Na–K ATPase of the sarcolemma preparation requires supporting ligands and is characterized by fast association and very slow dissociation in vitro. The second species of digitalis receptor does not require supporting ligands for ouabain binding and is characterized by slow association and fast dissociation. To determine which species of digitalis receptor is associated with the positive inotropic action of digitalis, ouabain washout experiments were conducted using various isolated canine myocardial preparations. Washout of the positive inotropic effects of 1.2–2.4 × 10−7 M ouabain gave half-life values of 1.5–2.0 h for the various myocardial preparations. [3H]ouabain dissociation from the second species of digitalis receptors gave half-life values of 1.7–1.8 h, whereas dissociation from the sarcolemma Na–K ATPase gave half-life values of 8.9–9.3 h for the various sarcolemma preparations utilized. Therefore, based on similarities in half-life values between ouabain inotropy and [3H]ouabain dissociation from the second class of digitalis receptors, it is postulated that the positive inotropic action of digitalis glycosides is associated with the second species of digitalis receptors in the sarcolemma and not with the digitalis inhibitory receptor of Na–K ATPase for nontoxic concentrations of digitalis.
Specific binding of [3H]phenytoin in the human brain
Authors: Spero L.
Published: April 2011

Competition between cold phenytoin and [3H]phenytoin binding was observed in normal human brain. Binding was observed in all areas examined. The highest number of sites was in the amygdala (a total of 717.71 fmol/mg protein) and the lowest in the Brodman area (BA) 4 of the motor cortex (153.91 fmol/mg protein) and cerebellar cortex (154.4 fmol/mg protein). In three areas, amygdala, cortex area BA 38 (inferior parietal lobe), and cortex area BA 8 (premotor cortex), two sets of binding sites were observed. In these areas the Kd for the higher affinity sites ranged from 35 to 116 nM, and for the lower affinity site, from 328 to 866 nM. In the four areas where only one binding site was observed the Kds ranged from 164 to 311 nM and the Scatchard plot was linear.
Energy intake and the nature of growth in low birth weight infants
Authors: Whyte R. K. , Bayley H. S. , Sinclair J. C.
Published: April 2011

Growth is accompanied by and depends on energy storage in growing tissue. The rate of energy storage in growing low birth weight infants depends on the rate of energy intake and on the rates of energy excretion and expenditure, both of which (on a body weight basis) are much higher than in adults, and both of which increase with increments of gross energy intake. Energy-balance studies of growing low birth weight infants on gross energy intakes approximating 500 kJ∙kg−1∙d−1 of mothers' milk or of infant formula indicate that the composition of extrauterine weight gain of the low birth weight infant differs from that of the fetus of similar gestation, in that the energy storage cost of growth is much higher. Attempts to increase metabolizable energy intake beyond 500 kJ∙kg−1∙d−1 by energy supplementation alone do not result in proportionately increased rates of weight gain; low birth weight formulae, in which energy, protein, and mineral contents are all increased can result in large weight gains with proportionate increases in rates of protein and fat accretion.
Peripheral and central mechanisms of the pressor response elicited by stimulation of the locus coeruleus in the rat
Authors: Drolet Guy , Gauthier Pierre
Published: April 2011

Electrical stimulation of the pontine nucleus locus coeruleus (LC) caused an increase of the arterial blood pressure in anesthetized rats, and elevated plasma noradrenaline (NA) and adrenaline (A) levels. The stimulation-induced pressor response was characteristically biphasic and consisted of a sharp rise in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulus. Bilateral adrenalectomy or adrenal demedullation completely blocked the secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the peripheral sympathetic vasomotor axons with intravenous 6-hydroxydopamine (6-QHDA). The active sites eliciting the secondary adrenomedullary pressor component appeared to be restricted to the nucleus LC, whereas the primary sympathetic vasomotor response could be elicited from sites in and around the nucleus. After brain transection at the midbrain level, stimulation of LC failed to evoke the adrenomedullary pressor response, while the sympathetic vasomotor component was not affected. Similarly, destruction of brain NA neurons by intraventricular administration of 6-OHDA did not change the sympathetic vasomotor response, but virtually abolished the adrenal response. The results demonstrate that the pressor response to stimulation of LC in the rat is due to both increased sympathetic vasomotor activity and CA released from the adrenal medulla. The study also provides evidence suggesting that the noradrenergic LC cell group play an important role in the activation of the adrenal medulla, but is not essential for the activation of the sympathetic vasoconstrictor fiber system.
Preliminary observations on the effects of stimulation of cardiac nerves in man
Authors: Murphy D. A. , Johnstone D. E. , Armour J. A.
Published: April 2011

The dorsal mediastinal cardiac nerves were stimulated in 20 patients undergoing coronary artery bypass surgery. In no instance was an untoward effect produced in any of the patients. Stimulation of a cardiac nerve increased heart rate in eight patients and slowed heart rate in eight patients. In 12 patients stimulation of a cardiac nerve increased mean aortic pressure while in 8 patients it was decreased, even though the patients were supported by a total body perfusion pump. In 11 patients stimulation of a cardiac nerve resulted in a decrease in the coronary artery bypass graft flow, even though aortic pressure was unchanged or increased. These preliminary results suggest that individual cardiac nerves in the dorsal mediastinum of man may be capable of modifying heart rate, total peripheral vascular resistance, or coronary artery resistance. Furthermore, they demonstrate that stimulation of human dorsal mediastinal cardiac nerves can be done without untoward effects and that such stimulations may be a means to investigate the complexity of neural regulation of the human heart.
Changes in isometric contractile properties of extensor digitorum longus and soleus muscles of C57BL/6J mice following denervation
Authors: Webster D. M. S. , Bressler B. H.
Published: April 2011

In this study, conducted on mice of the C57BL/6J+/+ strain, we investigated the differential effects of denervation on the isometric contractile properties of the extensor digitorum longus (EDL) and soleus (SOL) muscles. The contractile properties were studied at 1, 28, 84, and 210 days following unilateral section of the sciatic nerve at 12 weeks of age. When isometric tetanus tension was expressed relative to wet weight, the denervated SOL showed an earlier and more pronounced loss in tension generating capacity than the EDL. Both the denervated SOL and EDL showed potentiation of the twitch tension at 28 days postdenervation. The time to peak twitch tension (TTP) and the time to half-relaxation (1/2RT) were prolonged by 28 days postdenervation in both muscles. This trend continued to the oldest age-groups studied in the EDL, but reached an apparent plateau in the SOL at 84 days postdenervation. In response to fatigue, the denervated SOL showed a marked decrease in resistance to fatigue at 1 day but a relatively normal response thereafter, whereas the denervated EDL showed an increase in resistance to fatigue at and beyond the 28-day period. In spite of the fact that the total contraction time of both muscles increased following denervation, the predominantly oxidative SOL remained a slower contracting muscle than the more glycolytic EDL.
Inhibition of ACTH secretion in mouse pituitary tumor cells by activation of muscarinic cholinergic receptors
Authors: Heisler Seymour
Published: April 2011

Hormonally stimulated secretion of ACTH from AtT-20 mouse pituitary tumor cells is a cyclic AMP-mediated process. The presence of inhibitory cholinergic muscarinic receptors on these cells was recently reported, and in this study, the relationship between the activation of these receptors and the consequent inhibition of cyclic AMP formation and ACTH secretion was investigated. The muscarinic agent, oxotremorine, antagonized both cyclic AMP synthesis and ACTH secretion in response to corticotropin-releasing factor (CRF), vasoactive intestinal peptide, a 27-amino acid peptide with an N-terminal histidine and a C-terminal isoleucine amide, and forskolin. Other muscarinic agents, carbachol and bethanechol, had similar inhibitory effects. The cholinomimetics reduced basal (unstimulated) ACTH secretion without decreasing basal cyclic AMP levels, and also antagonized hormone release in response to cyclic AMP-independent agonists such as K+, A-23187, and phorbol ester. Scopolamine reversed the inhibitory effects of the muscarinic agents on basal and stimulated ACTH secretion and cyclic AMP formation. Increasing the extracellular calcium concentration reversed the muscarinic antagonism of basal and CRF-stimulated hormone release without affecting the cyclic AMP response. Pertussis toxin pretreatment attenuated the inhibitory effects of the muscarinic agents on forskolin-stimulated cyclic AMP synthesis and ACTH secretion as well as the inhibitory effect of carbachol on basal ACTH release. The data suggest that cyclic AMP is an essential mediator in the ACTH secretory pathway, but that an alternate cyclic AMP-independent ACTH pathway also exists in the clonal cells, and that both pathways may be modulated by a common postcholinergic receptor mechanism.
Activités des hydrolases rénales au cours du développement pré- et post-natal de la souris
Authors: Niederst C. , Dauça M.
Published: April 2011

The fetal and postnatal activity patterns of different hydrolytic enzymes (alkaline phosphatase, gamma-glutamyltransferase, trehalase, maltase, glucoamylase, lactase, and sucrase) have been examined in mouse renal homogenates. Alkaline phosphatase and gamma-glutamyltransferase activities presented approximately similar changes. They increased from 18 days of gestation up to 30 days after birth. These activities showed marked increases during the 3rd and 4th postnatal weeks. A similar important rise was observed for trehalase activity at the end of the suckling period. Maltase activity increased gradually after birth. Traces of lactase, sucrase, and glucoamylase activities were detected at each developmental stage.
Action of serotonin and norepinephrine on spinal motoneurones following blockade of synaptic transmission
Authors: Neuman R. S.
Published: April 2011

The actions of serotonin and norepinephrine were investigated on spinal motoneurones in isolated, hemisected rat and frog spinal cords. Serotonin and norepinephrine induced slowly developing depolarizations of spinal motoneurones which were frequently preceded by brief, low amplitude hyperpolarizations. Neither the depolarizations nor the hyperpolarizations were attenuated by 20 mM Mg2+ or tetrodotoxin, although synaptic transmission was blocked in both cases. It thus appears unlikely that the action of serotonin and norepinephrine on spinal motoneurone polarization and results from an indirect action via interneurones.
Symposium: Advances in Histamine Research
Authors: Wollin A.
Published: April 2011

The function of histamine in living organisms has interested investigators since its discovery shortly after the turn of the century and consequently has lead to the documentation of volumes of published data. It is rather surprising that the overall understanding of the function of histamine is still scant compared with other mediator substances discovered approximately during the same period of time. Perhaps the ubiquitous presence and the many effects of histamine in the body have diluted the efforts of investigators and have prevented a clear definition of all of its function. Both the local actions of histamine as a paracrine transmitter causing indirect responses as well as the multireceptor actions have no doubt also hampered the progress. It has been repeatedly stated that the development of the H2-receptor antagonists was one of the major accomplishments in the histamine field, which has lead to a new wave of increased histamine research activity and provided new meaning to earlier, unexplained data.In a series of symposia initiated by the Canadian Histamine Research Association, an attempt is being made to integrate previous findings with recent advances, and to familiarize those who are interested in histamine with the Canadian investigators and their research areas. The first symposium was held June 14, 1983, in conjunction with the Canadian Federation of Biological Societies and was published in this journal, June, 1984. The present symposium, the second in the series, deals with some aspects of earlier data in light of present knowledge and future prospects, as well as recent observations on receptor action and localization, and the mechanisms of action of drugs involved in the inhibition of histamine release. Because the local action of histamine has posed particular problems for the assessment of histamine concentration in relation to its action, it has become evident that not only histamine concentrations alone but also its metabolites would be of importance to demonstrate a correlation between endogenous histamine and its function. Thus, various assay procedures and methods are reviewed for the measurement of histamine metabolites to illustrate present capabilities in this field.The support for the symposium came from the Canadian Physiological Society, Smith Kline and French Canada Ltd., and Beckman Instruments Inc.
Hg2+-induced contracture in mechanically skinned fibers of frog skeletal muscle
Authors: Aoki Takako , Oba Toshiharu , Hotta Ken
Published: April 2011

In mechanically skinned fibers of the semitendinosus muscle of bullfrogs, we examined the role of membrane sulfhydryl groups on Ca2+ release from the sarcoplasmic reticulum (SR). Hg2+, a sulfhydryl reagent (20–100 μM), induced a repetitive contracture of skinned fibers, and this contracture did not occur in skinned fibers in which the SR had been disrupted by treatment with a detergent (Brij 58). Procaine (10 mM), Mg2+ (5 mM), or dithiothreitol (1 mM) blocked the Hg2+-induced contracture. Ag+ or p-chloromercuribenzenesulfonic acid produced similar contractures to that induced by Hg2+. We conclude that Hg2+ releases Ca2+ from SR of a skinned fiber by modifying sulfhydryl groups on the SR membrane, and suggest that the Ca2+ released by Hg2+ may trigger a greater release of Ca2+ from SR to develop tension.
Regional and subcellular distribution of enzymes of branched-chain amino acid metabolism in brains of normal and diabetic rats
Authors: Brosnan Margaret E. , Lowry Ann , Wasi Yasmin , Lowry Martin , Brosnan John T.
Published: April 2011

Branched-chain-amino-acid:α-ketoglutarate transaminase and branched-chain α-ketoacid dehydrogenase have been assayed in brains of control and of streptozotocin-induced diabetic rats. Enzyme activities were measured in five distinct regions of the brain: cerebellum, pons + medulla, midbrain, thalamus + hypothalamus, and telencephalon. Subcellular distribution of these enzymes in whole brain was assessed by fractionating brain homogenate into cytoplasm, free mitochondria, and synaptosomes. The following enzymes were used as markers: lactate dehydrogenase for cytoplasm, glutamate dehydrogenase for mitochondria, and glutamate decarboxylase for synaptosomes. The activity of the branched-chain amino acid transaminase in all brain regions was considerably higher than that of the branched-chain α-ketoacid dehydrogenase. While the highest activity of the transaminase occurred in brain-stem regions, the highest activity of the dehydrogenase was present in cerebellum and telencephalon. Diabetes did not affect the activity of the transaminase, but it caused a decrease in the total activity of the dehydrogenase in midbrain and in thalamus + hypothalamus. The transaminase was localized in the cytoplasmic fraction of whole brain, while the dehydrogenase was enriched in the free mitochondria.
Rapid axonal transport in Xenopus nerve in divalent cation free media
Authors: Snyder R. E. , Smith R. S.
Published: April 2011

An investigation was made of the effects of bathing media low in divalent cations on rapid axonal transport in the sciatic nerve of the amphibian Xenopus laevis. The anterograde transport of a pulse of [35S]methionine proteins was observed using a multiple proportional counter as the detector. Organelles undergoing anterograde and retrograde transport were detected by light microscopy. The structure of nerve fibres was examined by light and electron microscopy. There was no significant difference in the anterograde transport of proteins in nerves bathed in normal medium (NM) containing millimolar Ca2+ and Mg2+ and in those bathed in calcium-free medium (CaFM) containing Mg2+. The anterograde transport of labelled proteins continued at a normal velocity in nerves bathed in divalent cation free medium (DCFM) for at least 14 h. DCFM did cause some alterations in protein transport: the ratio of the plateau (following pulse passage) to the peak radioactivity was increased, the pulse amplitude decreased more rapidly, and the label continued to arrive at the distal end of the nerve for >16 h. Anterograde and retrograde organelle transport continued normally for periods of [Formula: see text] in fibres bathed in DCFM. All myelinated fibres became distorted within 4 h in DCFM. Similar distortion was rare in fibres bathed in CaFM. The results indicate that axonal transport in Xenopus is largely independent of lowered concentrations of divalent cations in the bathing medium. Those alterations in axonal transport that were produced by DCFM may have been secondary to morphological changes in the nerve fibres.
Studies of the role of gamma-aminobutyric acid in the hypothalamic control of feed intake in sheep
Authors: Girard C. L. , Seoane J. R. , Matte J. J.
Published: April 2011

Fourteen sheep were used to study the role of gamma-aminobutyric acid (GABA) on the hypothalamic control of feed intake. Injections (1 μL) of pentobarbital (262 nmol) into preoptic and paraventricular areas induced feeding in satiated sheep. Injections of GABA into the same loci gave variable results, probably because the neuronal and glial uptake of GABA limits its effects. Muscimol, a GABA agonist with a higher affinity for postsynaptic GABA receptors than GABA, injected at doses from 0 to 0.750 nmol, gave a cubic dose–response curve; the highest feed intake was measured at 0.5 nmol. The response induced by muscimol was blocked by preinjections of two GABA antagonists, picrotoxin and bicuculline, with picrotoxin being more effective than bicuculline. Muscimol responsive loci were identified mainly in the preoptic, paraventricular, and anterior hypothalamus. The data suggests that neurons sensitive to gamma-aminobutyric acid may be implicated in the control of feed intake in sheep.
Affinity of calcium channel inhibitors, benzodiazepines, and other vasoactive compounds for the nucleoside transport system
Authors: Hammond James R. , Williams Evan F. , Clanachan Alexander S.
Published: April 2011

There is evidence to suggest that several different groups of drugs including the so-called coronary vasodilators, benzodiazepines, and calcium channel inhibitors may owe their vasoactivity, in part, to the potentiation of the vasorelaxant effects of endogenous adenosine. To measure the affinity of some of these agents for the membrane-located nucleoside transport system, competition binding assays have been performed using the high-affinity radioligand [3H]nitrobenzylthioinosine (NBMPR). Experiments were performed on human erythrocytes and cardiac membranes from guinea pigs and rats. Recognized nucleoside transport inhibitors had high affinity (<50 nM) for NBMPR recognition sites associated with the nucleoside transporter complex in human erythrocytes, whereas calcium channel inhibitors and benzodiazepines had predominantly low affinity (> 1 μM). Although some recognized transport inhibitors, such as dipyridamole, show marked differences in affinity for NBMPR sites in guinea pig and rat tissues, benzodiazepines and calcium channel blockers displayed no such species selectivity and had low affinity (> 1 μM) for NBMPR sites in both guinea pig and rat cardiac membranes. Consequently, it is unlikely that agents such as benzodiazepines and calcium channel inhibitors cause significant inhibition of adenosine transport, and hence potentiate adenosine actions, at the concentrations required to induce effects through occupation of their respective, specific high-affinity sites.
Hyperglycemic effect of high doses of dobutamine in the rat: studies of insulin and glucagon secretion
Authors: Rousseau-Migneron Suzanne , Nadeau Sophie , Nadeau André
Published: April 2011

The influence of dobutamine on glucoregulation has been assessed in the rat during and after an intravenous infusion given at the following doses: 0, 0.1, 1.0, 10, 100, and 1000 μg∙kg−1∙min−1. Plasma glucose, insulin, and glucagon levels were measured at 15-min intervals in unanesthetized previously cannulated rats. Basal glucose levels were preserved with the ≤10 μg∙kg−1∙min−1 doses. At the ≥100 μg∙kg−1∙min−1 doses, a marked hyperglycemic effect was observed, partly attributable to some inhibitory effect of dobutamine on glucose-induced insulin secretion and to its stimulatory effect on glucagon secretion. Such data suggest that dobutamine may disturb the normal glucose homeostasis, particularly in situations of deficient insulin reserve.