bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of insulin deficiency, dietary protein intake, and plasma amino acid concentrations on brain amino acid levels in rats
Authors: Glanville N. Theresa , Anderson G. Harvey
Published: April 2011

The effect of diabetes (streptozotocin, 65 mg/kg ip), dietary protein intake (15–60%), and plasma amino acid concentrations on brain large neutral amino acid levels in rats was examined. After 20 days, the plasma concentrations of methionine and the branched chain amino acids (BCAA), valine, isoleucine, and leucine were increased in diabetic rats. In brain tissue, methionine and valine levels were increased but threonine, tyrosine, and tryptophan concentrations were depressed. Increased protein consumption promoted a diabetic-like plasma amino acid pattern in normal rats while enhancing that of diabetic animals. However, with the exception of threonine, glycine, valine, and tyrosine, there was little effect on brain amino acid levels. A good association was found between the calculated brain influx rate and the actual brain concentration of threonine, methionine, tyrosine, and tryptophan in diabetic animals. There was no correlation, however, between brain influx rate and brain BCAA levels. Thus, the brain amino acid pattern in diabetes represents the combined effects of insulin insufficiency and composition of the diet ingested on plasma amino acid levels as well as metabolic adaptation within the brain itself.
Cardiac myofibrillar creatine kinase is not influenced by hypothyroidism
Authors: Dowell Russell T. , Martin Anne F.
Published: April 2011

The cardiac myofibrillar component of the phosphorylcreatine shuttle mechanism enzymatically couples the functionally significant processes of energy utilization (ATPase) with substrate regeneration by creatine kinase (CK). Both components have isoenzyme forms that are transcriptionally regulated. Propylthiouracil-induced (PTU) hypothyroidism reduced rat cardiac contractile protein ATPase activity by shifting isomyosin predominance from the V1 to the V3 form. However, neither CK specific activity nor CK isoenzyme composition was altered by PTU treatment. Thus, myofibrillar components of the phosphorylcreatine shuttle, ATPase and CK, are not coordinately regulated under hypothyroid conditions.
Effects of thyroid and growth hormone deficiency, and food restriction on heart mass, with and without added stress (carboxyhemoglobinemia)
Authors: Penney David G. , Barthel Bernd G.
Published: April 2011

The roles of thyroid and growth hormone, and food restriction in maintenance of heart mass and in carbon monoxide-stimulated cardiac growth were examined. First, thyroidectomized and normal adult male rats inhaled up to 500 ppm CO in air for 42 days. Combined ventricular weights of thyroidectomized rats inhaling CO and air were 12 and 23% smaller than predicted, respectively, while the combined ventricular weight of normal rats inhaling CO was 29% larger than predicted. Thyroidectomy increased the mass of the left ventricle relative to the right ventricle; this was reversed by CO treatment. While the hematocrit increased in thyroidectomized–CO rats, it was lower than in normal–CO rats: likewise the hematocrit of thyroidectomized–AIR rats was lower than that of normal rats in air. Body weights of the thyroidectomized rats were 57% that of normals. As additional controls, two groups of normal rats (one AIR, one CO) were maintained at the same body weight as the thyroidectomized rats, by adjusting food intake. Combined ventricular weight was less than predicted in AIR rats and failed to increase in CO animals, while hematocrits were the same as normals in air and in CO. Serum thyroxine (T4) and growth hormone levels assayed in thyroidectomized rats were less than 15 and 25% of normal rats, respectively. Growth hormone levels were not altered by CO inhalation in thyroidectomized and in normal rats. Levels of both hormones were normal in food-restricted rats. While thyroidectomy produced cardiac atrophy, cardiac growth was stimulated by CO inhalation, although heart mass then only approached that of normals in air. Food restriction also produced cardiac atrophy, but CO inhalation failed to stimulate heart growth.
Release of atrial natriuretic peptide by atrial distension
Authors: Ledsome J. R. , Wilson N. , Courneya C. A. , Rankin A. J.
Published: April 2011

A heterologous radioimmunoassay was used to measure the concentration of immunoreactive atrial natriuretic peptide (iANP) in plasma from the femoral artery of eight chloralose anaesthetized dogs. Mitral obstruction which increased left atrial pressure by 11 cmH2O increased plasma iANP from 97 ± 10.3 (mean ± SE) to 135 ± 14.3 pg/mL. Pulmonary vein distension increased heart rate but did not increase plasma iANP. Bilateral cervical vagotomy and administration of atenolol (2 mg/kg) did not prevent the increase in iANP with mitral obstruction. Samples of blood from the coronary sinus had plasma iANP significantly higher than simultaneous samples from the femoral artery confirming the cardiac origin of the iANP. Release of iANP depends on direct stretch of the atrium rather than on a reflex involving left atrial receptors.
The effect of lidocaine on lysophosphatidylcholine-induced cardiac arrhythmias and cellular disturbances
Authors: Neufeld Karin J. , Lederman Cindy L. , Choy Patrick C. , Man Ricky Y. K.
Published: April 2011

The production of arrhythmias in the isolated heart by perfusion with lysophosphatidylcholine has been well documented. However, the role of the lysophospholipid as a physiological factor in the generation of cardiac arrhythmias is not clear. In this study, a pharmacological approach was used to delineate the physiological significance of lysophosphatidylcholine during this cardiac dysfunction. Lidocaine (5–20 mg/L) was found to be effective in the protection of the isolated rat heart from the lysophospholipid-induced arrhythmias at pharmacological concentrations. The effect of lidocaine in the protection of lysophospholipid-induced membrane dysfunction was studied with red blood cells. Lidocaine (2 mg/mL) protected red blood cells from hemolysis in the presence of lysophosphatidylcholine. Lidocaine did not inhibit the binding of the lysophospholipid to the red cell membrane, but inhibited hemolysis in a manner similar to cholesterol. The results are consistent with the postulate that lysophosphatidylcholine is a physiological factor in the pathogenesis of cardiac arrhythmias during myocardial ischemia.
The effect of tryptophan on biogenic amines in the hepatic portal circulation of the dog
Authors: Hussain M. N. , Sirek A. , Cukerman E. , Sirek O. V.
Published: April 2011

Mongrel dogs were fitted with indwelling hepatic portal catheters. After recovery from surgery, experiments were conducted in fasting, unrestrained, fully conscious, normal dogs which were accustomed to handling and withdrawal of blood samples. L-Tryptophan, a specific serotonin precursor, was injected into a saphenous vein, 10 μM/kg body weight, dissolved in saline. Plasma serotonin, dopamine, norepinephrine, and epinephrine were determined by radioenzymatic assays in blood samples withdrawn at frequent intervals for 2 h, simultaneously from the indwelling catheter and from a catheter temporarily inserted into a saphenous vein other than the one used for the injection of tryptophan. The injection of the amino acid caused a significant elevation of the concentration of platelet-free serotonin within 60 min and this was accompanied by a reduction in the concentration of the catecholamines, dopamine, norepinephrine, and epinephrine. The changes occurred only in the portal circulation and were not detected in peripheral blood samples. The results of these experiments indicate the existence of a cause and effect related interdependence between the splanchnic serotonergic and adrenergic systems in that the tryptophan-stimulated increase in serotonergic activity resulted in a concomitant reduction in gut adrenergic activity.
Action of agonists and antagonists on adrenergic receptors in isolated porcine coronary arteries
Authors: Horst Mark A. , Robinson Casey P.
Published: April 2011

The adrenergic receptors of porcine coronary arteries were investigated in helically cut strips of small (≤0.5 mm outer-diameter (od), medium (0.8–1.2 mm od), large (1.5–2.5 mm od), and very large (>4 mm od) coronary arteries. Both the beta1 agonist dobutamine and the beta2 agonist terbutaline relaxed coronary arteries partially contracted by 25 mM of KCl. Dobutamine contracted small coronary arteries at 10−5 M concentrations, then relaxed them at 10−4 M. The beta1-adrenoceptor antagonist metoprolol contracted coronary arteries relaxed by either dobutamine or terbutaline, but the beta2 antagonist H35/25 did so only in high and probably nonselective concentrations. Alpha1-adrenoreceptor stimulating concentrations of phenylephrine did not contract any of the arteries. Metoprolol and high concentrations of H35/25 further contracted large coronary arteries partially contracted by 25 mM potassium. These contractions were blocked by verapamil and papaverine but not by atropine, phentolamine, yohimbine, mepyramine, or methysergide. This seems to indicate that beta-adrenergic receptors in porcine coronary arteries are beta1-receptors, or closely resemble beta1-receptors. They differ from many other beta1-receptors, however, in that they are stimulated by terbutaline. Alpha1 adrenoreceptors seem not to be present in these porcine coronary arteries to a significant extent. Metoprolol and high concentrations of H35/25 have a direct contractile effect in large porcine coronary artery that is not mediated by alpha-adrenergic, muscarinic, histaminergic, or serotonergic receptors but requires verapamil-sensitive calcium.
Distinct hydrodynamic forms of the insulin receptor: electrophoretic analysis of the RI and RII species
Authors: Maturo III J. M. , Hollenberg M. D.
Published: April 2011

In previous work, we identified two insulin receptor species, RI (KAV = 0.31) and RII (KAV = 0.53), that could be separated by gel filtration on Sepharose 6B. In the present study, we sought to establish that these two receptor species do represent larger (RI) and smaller (RII) oligomeric forms of the receptor, rather than representing receptor species separated from each other by differential adsorption to the Sepharose matrix. Receptor solubilized from isolated human placenta membranes was purified by lectin–and insulin–agarose chromatography and was radiolabeled with carrier-free 125I. The labeled receptor was separated by Sepharose 6B gel filtration into two fractions (peak I, (KAV = 0.31; peak II. KAV = 0.53), was immunoprecipitated by anti-insulin receptor antibody, and was analysed by electrophoresis in nonreducing polyacrylamide slab gels. The auto-radiograms of the gels indicated that peak I (KAV = 0.31, RI receptor form) contained a number of receptor species of 240 000 daltons or greater, whereas peak II (KAV = 0.53, RII receptor form) contained mainly receptor species of 210 000 daltons or smaller. In particular, large amounts of a 90 000 dalton species (presumably free receptor β-subunit) were present in peak II. Incubation of the material obtained from peak I with insulin resulted in a change in the electrophoretic pattern, which became identical with that observed for material recovered from peak II. We conclude that the RI and RII hydrodynamic forms of the receptor previously described correspond to larger (RI) and smaller (RII) oligomeric forms of the receptor, and that the RII receptor form, which can result from the binding of insulin to the RI form, contains a large proportion of free receptor β-subunit.
EGTA-sensitive and -insensitive forms of particulate adenylate cyclase in rat cerebral cortex: regulation by divalent cations and GTP
Authors: Sulakhe P. V.
Published: April 2011

Interactions of several divalent cations (Mn2+, Ca2+, Co2+, Sr2+, and Zn2+) with EGTA-inhibitable adenylate cyclase were investigated in washed membranes (particles) isolated from the gray matter of rat cerebral cortex. The EGTA-inhibitable (called sensitive) enzyme activity was assayed in the presence of Triton X-100 since this detergent caused a marked increase (up to 20-fold) in the enzyme activity. The effects of various divalent metals (all added as chloride salt) indicated the presence of two distinct sites called site I and site II. At low concentrations (less than micromolar) Mn2+, Co2+, and Ca2+ increased (up to 10-fold) the enzyme activity to the same extent and appeared to act via binding to site I (high affinity site). The rank order of affinity was Mn2+ ≥ Co2+ > Ca2+. Zn2+ showed the highest affinity and Sr2+ the lowest towards binding to site I; both these metals increased the enzyme activity to lesser extents than Mn2+, Co2+, or Ca2+. GTP was not required for the stimulation of this enzyme by low concentrations of Ca2+. The interaction of Mn2+ with site II (low affinity site) caused further increase in the enzyme activity, whereas Co2+, Ca2+, and Sr2+ were inhibitory at concentrations >10 μM. Isolated fraction contained loosely and tightly associated pools of calmodulin. Myelin basic protein, but not calcineurin, inhibited the EGTA-sensitive adenylate cyclase activity. The EGTA-insensitive enzyme activity was increased by norepinephrine by mechanisms that depended on GTP and was inhibited by Ca2+. The stimulation of the EGTA-insensitive enzyme modulated the Mg2+ requirement such that Mg2+ binding to the low affinity site (site II) apparently occurred with higher affinity. The likely significance of these results is discussed with regard to (i) the presence of two classes of adenylate cyclase in rat cerebral cortex gray matter and (ii) the regulation of their activities by calmodulin-requiring and GTP-requiring mechanisms.
Direct determination of the contractility of the guinea pig gallbladder: a new in vivo model
Authors: Pomeranz I. S. , Davison J. S. , Shaffer E. A.
Published: April 2011

In vivo methods to study gallbladder contractility either equate gallbladder emptying with contraction or have relied on changes in gallbladder intravesicular pressure to reflect active transmural tension. We therefore devised an animal model in which the contractile force of the intact gallbladder is measured directly while the blood and neural supply remains uncompromised. Under general anesthesia one pole of the guinea pig gallbladder is anchored to the sternum and the other connected to a force displacement transducer. Any contraction–relaxation between these two points is recorded. This model was validated by measuring gallbladder response to both neuronal and humoral stimulation. Nerve stimulation was accomplished by means of two silver collar electrodes placed in contact with the cystic duct. With nerve stimulation, a frequency (0.5–10 Hz) or amplitude (1–10 V) dependent contraction occurred. Intravenous bethanechol (10 × 104 ng∙kg−1∙h−1) and cholecystokinin (3 × 104 ng∙kg−1∙h−1) both induced dose-dependent gallbladder contraction. This model should prove useful in assessing the physiologic control of gallbladder contraction.
Catecholamine release and ventricular arrhythmias during coronary occlusion and reperfusion in the dog
Authors: Godin Diane , Campeau Nicole , Nadeau Réginald , Cardinal René , Champlain Jacques de
Published: April 2011

In anesthetized dogs, 60-min occlusions of either the proximal (n = 14), distal (n = 8) left circumflex (LCX), or left anterior descending (LAD, n = 10) arteries were followed by reperfusion. Coronary sinus and aortic norepinephrine and epinephrine plasma concentrations were measured. The ventricular arrhythmias were ventricular premature depolarizations (VPDs), unsustained ventricular tachycardia (VT) ([Formula: see text] and <20 VPDs), sustained VT ([Formula: see text] VPDs), and ventricular fibrillation (VF). A gradual twofold increase (p < 0.05) in myocardial norepinephrine overflow followed occlusion in all three groups. The increases in the amounts of norepinephrine released in the coronary sinus blood during reperfusion were significant and proportional to the size of the occluded area: proximal LCX, from 0.236 ± 0.038 to 1.528 ± 0.490 ng/mL of plasma (p < 0.001); LAD, from 0.180 ± 0.027 to 0.795 ± 0.286 ng/mL (p < 0.05); distal LCX, from 0.215 ± 0.039 to 0.404 ± 0.110 ng/mL (p < 0.05). Aortic epinephrine concentrations were significantly increased only by LAD occlusion; at 15 min, the value had increased to 0.187 ± 0.053 ng/mL from an initial value of 0.069 ± 0.029 ng/mL (p < 0.001). Two phases of ventricular arrhythmias followed both occlusion and reperfusion. Phase 1 postocclusion was characterized by VPDs and phase 2 by VPDs and unsustained VT. Sustained VT was seen only in phase 1 postreperfusion, whereas unsustained VT was seen in phase 2. VF was seen in 50, 35, and 25% of the dogs with proximal LCX, LAD, and distal LCX occlusion and reperfusion. Sustained VT occurred in 90, 45, and 30% of the dogs during proximal LCX, LAD, and distal LCX reperfusion. In conclusion, postocclusion and phase-2 reperfusion arrhythmias did not appear to be related to either increased coronary sinus norepinephrine or aortic epinephrine concentrations. However, the occurrence and time course of reperfusion-sustained VT closely followed those of norepinephrine washout. Furthermore, both the magnitude of norepinephrine release and the incidence of sustained VT appeared to be proportionally related to the size of the hypoperfused ventricular area.
Thermoregulatory responses of dystrophic hamsters to changes in ambient temperatures
Authors: Desautels M. , Dulos R. A. , Thornhill J. A.
Published: April 2011

The ability of dystrophic hamsters to maintain their body temperature despite abnormal muscle and brown adipose tissue, two organs involved in thermoregulation, was evaluated. Dystrophic hamsters (CHF 146) between the ages of 30 and 160 days kept at 21 °C had core (rectal) temperatures (TR) that were 0.5–1.5 °C lower than Golden Syrian controls. The reduced core temperatures of dystrophic hamsters were unlikely the result of an incapacity to generate heat since the dystrophic hamsters were able to maintain their TRs during 3 h of acute cold stress (4 °C) and to adapt to prolonged cold exposure. However, TRs of cold-acclimated dystrophic hamsters were still 1 °C below TRs of cold-acclimated control animals. By contrast, increasing the ambient temperature raised TRs of both normal and dystrophic hamsters. When kept at 32 °C overnight, the TRs of dystrophic hamsters remained significantly below those of control animals. When heat-exposed dystrophic hamsters were returned to 21 °C, their TRs returned to values significantly lower than those of control hamsters. Thus, dystrophic hamsters showed a capacity to thermoregulate, like control hamsters, but appeared to do so at a lower temperature. The reduced core temperatures of dystrophic hamsters kept at 21 °C cannot be explained by a reduction in metabolic activity since newborns and 30- and 140-day-old dystrophic hamsters had rates of oxygen consumption [Formula: see text] and carbon dioxide production [Formula: see text] that were similar to those of controls. These results suggest that the thermoregulatory set point may be altered in dystrophic hamsters.
Adenine nucleotide synthesis from inosine during normoxia and after ischaemia in the isolated perfused rat heart
Authors: Aussedat J. , Verdys M. , Rossi A.
Published: April 2011

[14C]inosine in a range of concentrations of 20 μM to 1 mM was administered-to the isolated perfused rat heart for 30 min. The incorporation of the nucleoside into myocardial adenine nucleotides increased for extracellular concentrations of the precursor up to 50 μM, reaching a plateau at 60 nmol∙g−1∙30 min−1 with concentrations ranging between 50 and 200 μM. The supply of 500 μM and 1 mM of inosine induced a further increase in cardiac adenine nucleotide synthesis to about 200 nmol∙g−1∙30 min−1. When supplied during low flow ischaemia (0.5 mL∙min−1, 30 min.), 1 mM of inosine protected the heart against ATP degradation, while 100 μM of inosine was inefficacious. In the presence of 1 mM of inosine on reperfusion the adenine nucleotide content of the heart was similar to that observed in the absence of the nucleoside. The incorporation of [14C]inosine into adenine nucleotides was, in this last condition, below the value measured before ischaemia. Inosine administration was effective in protecting the heart against ischaemic breakdown of glycogen and favoured postischaemic restoration of glycogen stores.
The significance of adrenaline-induced potentiation of electrogenic sodium pumping in bullfrog sympathetic ganglia
Authors: Smith Peter A. , Dombro Kochu-Rani
Published: April 2011

Two different electrophysiological responses in amphibian sympathetic ganglia were studied by means of the sucrose gap technique; (i) the potassium-activated hyperpolarization (KH) which serves as an index of electrogenic Na+ pumping, and (ii) the hyperpolarization induced by adrenaline (AdH). Under appropriate experimental conditions, 0.1 μM adrenaline potentiated the KH to 121.5 ± 7.5% of control (n = 7). This potentiation was blocked by both yohimbine (50 nM) and prazosin (1 μM) but not by propranolol (1 μM). Clonidine (10 nM) potentiated the KH to 113.5 ± 3.4% of control (n = 5), whereas methoxamine (0.1 μM) was ineffective. Several lines of evidence argued against the hypothesis that the AdH may be generated, in whole or in part, by stimulation of the Na+ pump. For example, (i) the AdH was sometimes completely unaffected when the KH was blocked by ouabain, and (ii) the AdH was eliminated by 2 nM Ba2+ even though this cation enhanced membrane hyperpolarization accompanying electrogenic Na+ pumping. These results imply that the electrogenic Na+ pump is not involved in the short-term electrophysiological effects of catecholamines. Despite this, it is possible that the homeostasis of Na+ and K+ in nerve may be regulated by α-adrenergic mechanisms.
Peripheral vascular responses to hypoxic hypoxia after aortic denervation
Authors: King C. E. , Cain S. M. , Chapler C. K.
Published: April 2011

We wished to see whether aortic chemoreceptors and other vagal afferent traffic played an essential role in the circulatory adjustments to hypoxic hypoxia. Aortic chemoreceptors were denervated (AD) in one group (n = 6) of anesthetized dogs, bilateral cervical vagotomy (V) was done on a second group (n = 6), and a third group (n = 6) was sham-operated to serve as a control. Venous outflow from the left hindlimb was isolated. After a 20-min control period of ventilation with room air, the animals were ventilated for 60 min with 9% Q2 in N2. Arterial, mixed venous, and hindlimb venous blood samples were taken every 20 min. The cardiac output response to hypoxic hypoxia was attenuated at 40 and 60 min in both the AD and V groups (p < 0.05). Hindlimb blood flow increased equally in all three groups during hypoxia. The pressor response at the onset of hypoxia (20 min) was abolished in the AD and V groups, but mean arterial pressure fell to similar levels in all three groups by 60 min of hypoxia. We concluded that reflex aortic chemoreceptor stimulation during hypoxia augmented cardiac output mostly by effects on the venous side of the circulation but played no role in skeletal muscle vascular responses to hypoxic hypoxia.
Effect of endurance swimming on rat cardiac myofibrillar ATPase with experimental diabetes
Authors: Belcastro A. N. , Maybank P. , Rossiter M. , Secord D.
Published: April 2011

Diabetes is characterized by depressed cardiac functional properties attributed to Ca2+-activated ATPase activity. In contrast, endurance swimming enhances the cardiac functional properties and Ca2+-activated myofibril ATPase. Thus, the purpose of this study was to observe if the changes associated with experimental diabetes can be ameliorated with training. Diabetes was induced with a single i.v. injection of streptozotocin (60 mg/kg). Blood and urine glucose concentrations were 802 ± 44 and 6965 ± 617 mg/dL, respectively. The training control and training diabetic animals were made to swim (±2% body weight) 4 days/week for 8 weeks. Cardiac myofibril, at 10 μM free Ca2+ concentration was reduced by 54% in the sedentary diabetics compared with sedentary control animals (p < 0.05). Swim training enhanced the Ca2+-activated myofibril ATPase activities for the normal animals. The diabetic animals, which swam for 8 weeks, had further reduced their Ca2+-activated myofibril ATPase activity when compared with sedentary diabetics (p < 0.05). Similarly, the Mg2+-stimulated myofibril ATPase activity was depressed by 31% in diabetics following endurance swimming. It is concluded that the depressed Ca2+-activated myofibril ATPase activity of diabetic hearts is not reversible with endurance swimming.
The relationship between the thermogenic response of brown adipose tissue and age during noradrenaline infusion in the young rabbit
Authors: Harris W. H. , Foster D. O. , Nadeau B. E.
Published: April 2011

This work was undertaken to determine if the thermogenic activity of brown fat decreased with age in young rabbits despite the morphological evidence indicating persistence of the brown adipocytes at 4 weeks of age. Data obtained by infusing five doses of noradrenaline and measuring oxygen consumption were used to construct cumulative dose–response curves for five age groups between 3 and 32 days of age. Blood flow to brown fat and other tissues was measured by the microsphere method at 1 and 3 weeks of age. The noradrenaline-induced increase in oxygen consumption when expressed as a percentage of resting oxygen consumption in millilitres per 100 g of body weight decreased (p < 0.05) with age. However, the absolute noradrenaline-induced increase in metabolic rate (millilitres per minute) increased with age. Total blood flow to brown fat (millilitres per minute) during noradrenaline infusion was unchanged between 1 and 3 weeks of age, but when the blood flow was expressed in millilitres per minute per gram of tissue flow decreased significantly (p < 0.05) probably because of infiltration of brown fat with white fat. These data suggest that the amount of brown fat and its thermogenic capacity remain relatively constant between 1 and 3 weeks of age, but as a thermogenic organ, brown fat becomes proportionally less effective with age because of the large increase in body mass.
The calcium channel agonist, Bay K-8644, antagonizes effects of diacetyl monoxime on cardiac tissues
Authors: Sada Hideaki , Sada Shigiko , Sperelakis Nicholas
Published: April 2011

Effects of a novel slow channel activator, Bay K-8644 (Bay K), were studied on slow action potential (APs) in young and old embryonic chick hearts, and on its antagonism of the effects of diacetyl monoxime (DAM). The slow APs of young hearts are mediated by slow Na+ channels, whereas those of old hearts are mediated by slow Ca2+ channels. In slow APs of old (13–18 days old) embryonic chick hearts superfused with a high (22 mM) K+ solution, Bay K (10−6 M) gradually increased the amplitude, maximum rate of rise [Formula: see text], and duration of the slow APs. The actions of Bay K persisted for a long time (>30 min) after washout of the drug. DAM (10 mM) depressed the [Formula: see text], duration and amplitude of the slow APs. Some of the changes in slow AP parameters produced by DAM, e.g., [Formula: see text] decrease, were antagonized by the addition of Bay K (10−6 M). In 3-day-old embryonic chick hearts, Bay K potentiated the slow APs and DAM depressed them; Bay K antagonized these effects of DAM. Thus, the actions of Bay K and DAM are likely to be produced, respectively, via the activation and depression of slow Ca2+ channels in old embryonic chick hearts. In addition, the drugs seem to influence slow Na+ channels found in young embyronic chick hearts.
Stimulation of an N-ethylmaleimide-sensitive ATPase in the collecting duct segments of the rat nephron by metabolic acidosis
Authors: Garg Lal C. , Narang Neelam
Published: April 2011

A plasma membrane ATPase sensitive to inhibition by N-ethylmaleimide (NEM) and insensitive to inhibition by oligomycin and ouabain has been shown to be involved in acidification of urine in the turtle bladder. The activity of this NEM-sensitive ATPase was determined in four types of distal nephron segments of normal rats and in rats treated with ammonium chloride. The enzyme activity was determined by a fluorometric micromethod in which ATP hydrolysis was coupled to NADH oxidation. Significant activities (10–35 pmol ADP∙min−1∙mm−1) of NEM-sensitive ATPase were present in the distal convoluted tubule (DCT) and in the cortical and outer and inner medullary collecting duet segments of normal rats. In metabolic acidosis produced by ammonium chloride treatment (plasma CO2 content = 15.3 ± 0.8 mequiv./L), the NEM-sensitive ATPase activity was increased significantly (60–100%) in the collecting duct segments without showing a significant change in the enzyme activity in the DCT. Our data are consistent with the hypothesis that a plasma membrane H+-ATPase (inhibited by NEM but not by oligomycin or ouabain) is involved in H+ secretion in the mammalian collecting duct.
Retarded recovery of excitability and twitches of frog toe muscles after K-induced depolarization (slow inactivation) in the presence of alkyl amphipaths
Authors: Foulks James G. , Morishita Lillian
Published: April 2011

Alkyl amphipaths resemble conventional local anesthetics in their ability to retard the recovery of excitability and twitch tension after depolarization at high Ko, an effect that is attributed to slow inactivation of potential-dependent sodium channels. The similar effect of low temperature offers an explanation for its ability to enhance the frequency-dependent effects of these agents.
Bromobenzene causes Clara cell damage in mice
Authors: Forkert P. G.
Published: April 2011

The oral administration of a single dose of bromobenzene (5 mmol/kg) causes cellular damage in the lungs of C57B1/6 male mice. At 24 h following treatment with bromobenzene. Clara cells of the bronchiolar epithelium demonstrated necrosis; endoplasmic reticular cisternae were extensively dilated, and degenerated membranes were present in the cytoplasmic matrix as electron-dense tubular aggregates. The ciliated cells which were interspersed among the Clara cells, remained unaffected. The morphologic alterations produced by bromobenzene and the target cell are similar in character to the pulmonary lesions produced by administration of other aromatic and aliphatic halogenated hydrocarbons.
The 1985 Upjohn Award Lecture.: Tolerance, learning, and neurochemical adaptation
Authors: Kalant H.
Published: April 2011

Alcohol or drug tolerance has been viewed traditionally as a homeostatic response to a direct chemical action of the agent on the neuron. This concept has undergone major modification as a result of recent observations that behavioral and environmental factors can alter markedly the tolerance developed to the same drug regimen. Obligatory task performance under the influence of the drug, classical conditional stimuli in an environment habitually associated with drug administration, previous exposure to a tolerance-producing regimen, and environmental modification of the expression of the drug's effect can all influence dramatically the degree of tolerance produced by a given dosage. Attempts to identify possible cellular mechanisms of tolerance development are illustrated by a review of studies on the relations between ethanol tolerance and changes in the neuronal membrane Na+–K+ ATPase and its interaction with ethanol and norepinephrine, hippocampal serotoninergic systems and their interaction with a vasopressin derivative, a membrane-bound calcium- and calmodulin- dependent kinase, and hypothalamic–hypophyseal endorphin-producing systems. None of these studies or other similar ones, whether correlational or interventional in nature, has yet provided full and credible explanations of the effects of behavioral and environmental factors on tolerance development. Finding such explanations is the major current challenge in the neurobiology of tolerance.
Effect of verapamil on ventilation and chemical control of breathing in anesthetized rats
Authors: Chapman Richard W.
Published: April 2011

The calcium channel blocker, verapamil (0.1–1.0 mg/kg, i.v.) was administered to anesthetized rats to determine its effects on ventilation and on ventilatory responses to hypoxia and CO2. Verapamil produced a dose-dependent increase in tidal volume (VT) and a decrease in respiration rate (f). The bradypnea due to verapamil was characterized by an increase in expiratory duration (TE) and no change of inspiratory duration (TI). Verapamil produced similar changes in VT and f in vagotomized rats. The increase in respiration rate and minute volume due to hypoxia were inhibited by verapamil (0.5 and 1.0 mg/kg) but the increase in tidal volume due to hypoxia was depressed only with the 1.0 mg/kg dose. On the other hand, the increase in VT due to breathing CO2 was not changed by verapamil (0.1–1.0 mg/kg), but depression of the respiratory frequency response to CO2 occurred with 1.0 mg/kg of verapamil. These results indicate that verapamil produced slow, deep breathing and these responses were not mediated by vagal mechanisms. Ventilatory responses to hypoxia were depressed by verapamil. However, since the calcium blocker demonstrated no effect on the VT-CO2 relationship, verapamil did not change ventilatory chemosensitivity to CO2. The data also suggest that mechanisms governing the control of respiratory frequency are more sensitive to verapamil than tidal volume responses.
The aging gut
Authors: Thomson A. B. R. , Keelan M.
Published: April 2011

A spectrum of changes occurs in the function of the gastrointestinal tract throughout the life of the animal. With aging, there is a decline towards newborn levels of the villus surface area and brush border membrane markers, but the absorption of some nutrients continues to increase (such as glucose and vitamin), whereas the absorption of some nutrients falls (such as cholesterol and fatty acids). Clearly there is a distinction between age-related alterations in intestinal form and function, and some of the enzyme- or carrier-mediated changes are substrate specific. With aging, the structure and brush border membrane composition of the intestine tends to regress towards newborn levels. It remains to be clarified whether these changes are a benefit to the animal, whether they represent a degeneration of normal function, and whether these changes are the cause or the effect of various age-related alterations in metabolic and physiological function.
Increased phenylalanine incorporation in regenerating skeletal muscle grafts
Authors: Schwartz Jessica , Wiesen Jane , Carlson Bruce , Yamasaki L. , Moore M. , Womble Mark
Published: April 2011

Skeletal muscle regenerates following grafting, but little is known about protein synthesis and its regulation during regeneration. We determined the sequence of changes in protein synthesis in rat extensor digitorum longus (EDL) muscle by the measurement of phenylalanine (Phe) incorporation into muscle protein at various times after grafting. Compared with control EDL, Phe incorporation in grafts doubled in 1 day, was four- to eight-fold greater from days 2 to 10 after grafting, and then subsided. Tissue mass (wet weight) increased rapidly from days 7 to 20 in EDL grafts. The maximal increase in protein synthesis occurred 7–10 days after grafting, whether or not the nerve was left intact. Autoradiography indicated that incorporated radioactivity was associated with regenerating muscle fibers on day 10. Deficiencies of insulin, pituitary or testicular hormones, or chronic in vivo administration of insulin, growth hormone, testosterone, or tri-iodothyronine did not substantially alter the elevation in incorporation of the Phe into muscle protein 10 days after grafting. The breakdown of EDL protein, measured in vitro simultaneously with protein synthesis, was increased five-fold, and overall protein degradation was elevated six-fold 10 days after grafting. These findings indicate that Phe incorporation is rapidly elevated following grafting of the EDL, and that by days 7–10 reflects synthesis in regenerating muscle fibers. The increase in protein synthesis associated with muscle regeneration at this time appears to be independent of innervation and anabolic hormones.
Effects of ouabain on calcium paradox in rat hearts
Authors: Singh R. P. , Schellenberg D. , Weinberg L. , Singal P. K.
Published: April 2011

The effects of ouabain (10−7 to 10−5 M) on the interrelationship between cell–cell contacts, resting tension, and creatine phosphokinase (CK) leakage owing to myocardial cell injury during Ca2+ paradox were studied in isolated perfused rat heart preparations. After perfusing for 15 min with Ca2+-containing medium, hearts were perfused for 5 min with Ca2+ -free medium followed by a reperfusion with Ca2+-containing medium for 5 min. This resulted in a transient increase in resting tension and a substantial release of CK into the perfusate during the calcium reperfusion period. These changes were accompanied by extensive structural damage in the myocardial cell, including formation of contraction bands, swelling of the mitochondria, and cell–cell separation. Inclusion of 10−5 M ouabain for 5 min in the Ca2+-containing perfusion medium prior to the start of Ca2+-free perfusion resulted in a higher and sustained resting tension that was accompanied by a reduced loss of CK from the heart during Ca2+ reperfusion. In a histological examination of these ouabain exposed hearts, most of the structural changes owing to calcium paradox were apparent, but the cell–cell contacts were maintained. The results are consistent with the hypothesis that the loss of cell–cell contacts in the intercalated disc during the occurrence of Ca2+ paradox may be the cause of the delayed decline in the resting tension and is only partially responsible for the loss of CK. These differences in myocardial changes during Ca2+ paradox with or without ouabain may be due to the retention of calcium at certain crucial sites under the influence of ouabain.
Hormonal and metabolic responses to intracarotid and intrajugular infusion of β-endorphin in normal dogs
Authors: El-Tayeb K. M. A. , Gauthier C. J. T. , Brubaker P. L. , Lickley H. L. A. , Vranic M.
Published: April 2011

The hormonal and metabolic responses of β-endorphin infused cephalad into the carotid artery, or via the jugular vein, were examined in 10 normal dogs. The intracarotid administration of β-endorphin resulted in significant increases in plasma glucagon, adrenocorticotropin, and Cortisol levels. Hepatic glucose production increased only transiently and there was no significant change in glucose disappearance or plasma glucose concentrations. Infusion of β-endorphin in the jugular vein gave rise to significant increases in glucagon and Cortisol levels and to a transient increase in plasma epinephrine. Although no significant changes in glucose kinetics could be demonstrated, there was a slight transient decrease in plasma glucose concentrations. In conclusion, both intracarotid and intrajugular infusions of β-endorphin stimulated glucagon secretion independent of circulating catecholamines, and increased Cortisol release, probably through activation of the pituitary–adrenocortical axis.
Effect of nifedipine on calcium-induced contractions to potassium in the aorta and mesenteric arteries of spontaneously hypertensive and normotensive rats
Authors: Kannan M. S. , Seip A. E. , Crankshaw D. J.
Published: April 2011

Graded contractions to cumulative additions of calcium in the presence of KCl were obtained in strips of aorta and mesenteric arteries of normotensive (WKY) and spontaneously hypertensive (SHR) rats. In calcium-free medium, a maximally effective concentration of KCl produced a response that was larger in the mesenteric arteries (43–51% of control) than in the aorta (12–14% of control). The calcium channel blocker nifedipine (NFD, up to 10−7 M) did not significantly alter these calcium-insensitive responses. The Ca2+-induced responses were inhibited by NFD, in a concentration-dependent fashion, in both vessel types of WKY and SHR rats. The aortic responses were more sensitive to inhibition by NFD than the responses of mesenteric arteries. Moreover, the aortic responses of WKY were inhibited to a greater extent than those of the SHR. The results suggest: (a) a differential calcium dependence of contractions to KCl in the vessels studied; (b) that aortic responses are dependent on NFD-sensitive voltage-sensitive Ca2+ channels to a greater extent than the responses of mesenteric arteries; and (c) that hypertension results in a decreased sensitivity of the aorta Ca2+ channels to NFD.
Symposium Cholinergic Mechanisms: I. Function and Dysfunction of Cholinergic Neurones: II. Neurotoxicity Associated with Altered Cholinergic Function
Authors: Boegman Roland , Collier Brian
Published: April 2011

The objective of these two symposia was to summarize some of the more recent advances relating to the neurobiology of cholinergic synaptic transmission, with particular emphasis on presynaptic function and dysfunction.For many years productive studies of acetylcholine metabolism were sustained by the physiological importance of this neurotransmitter. More recently research upon cholinergic mechanisms has been stimulated by the association of cholinergic dysfunction with disorders of the nervous system, particularly those related to cognitive dysfunction. The association between central cholinergic hypofunction and memory deficits was suggested by studies of the effects of antimuscarinic drags (e.g., Drachman and Leavitt 1974), and particularly, by the association between loss of choline acetyltransferase activity and clinical and neuropathological signs of Alzheimer's disease (Bowen et al. 1976). Before effective therapy for such dysfunction can be approached with any rationale, it is necessary to understand the normal functional regulation of central cholinergic neurones of this transmitter turnover; the testing of therapeutic measures requires animal models.The first symposium includes presentations of the neuropathology of Alzheimer's disease, about the regulation and pharmacology of central cholinergic systems, and on the organization and regulation of transmitter synthesis and release. The second symposium concentrates upon the use of neurotoxins as tools to produce disorders of cholinergic function in animal models that might resemble human dysfunction.The use of natural substances such as toxins and venoms for therapeutic applications goes back to the beginning of medicine. However, the application of toxins as tools in physiological research marked a turning point in biological research. More than a century after Claude Bernard (1856) demonstrated that curare acts at the neuromuscular junction, curare is still being used as a tool to elucidate the most basic aspects of excitability and of synaptic transmission. The selectivity of neurotoxins for certain molecules or receptors and the possibility of handling and recognizing the toxins bound to their receptors are two most valuable advantages of these molecules for neurobiologists.The use of certain excitatory amino acids as selective neurotoxins resulted in part from the following observations: firstly, that excitatory acidic amino acids are neurotoxic when administered systemically to immature rodents (Lucas and Newhouse 1957), and secondly, that glutamic and aspartic acids act as neurotoxicants in the mammalian central nervous system (Curtis and Watkins 1960). The usefulness of excitotoxins in lesioning techniques became apparent following the observation that selective neuronal degeneration occurs near the site of injection while sparing axons of passage (Olney 1978).
Relationships between cardiac hyperactivity, oxygen tension, and release of vasodilator material in coronary autoregulation of guinea-pig hearts
Authors: Broadley Kenneth J. , Rothaul Alan L.
Published: April 2011

Increases in cardiac activity induce autoregulatory coronary vasodilation. The intermediate steps which trigger this process are thought to be myocardial hypoxia which induces the release of vasodilator mediator(s). The present study examines the relationships between mechanical activity, oxygen tension, and release of vasodilator material in isolated perfused hearts. Guinea-pig isolated hearts were perfused in series, the effluent from donor hearts being regassed prior to entry to recipient hearts. Histamine (1 μg) and isoproterenol (10 ng) increased the rate and tension of donor hearts and produced predominant coronary vasodilator responses which were followed by the appearance of vasodilator material in the recipient (falls in perfusion pressure, 9.8 ± 1.1 and 9.1 ± 2.5 mmHg) (1 mmHg = 133.322 Pa). Exposure of donor hearts to hypoxia also caused vasodilatation and release of vasodilator material (fall in pressure, 11.4 ± 1.6 mmHg). Pacing-induced tachycardia (6 Hz) of donor hearts promoted the release of vasodilator material, the fall in recipient heart pressure being 11.5 ± 1.8 mmHg. This was abolished by β-adrenoceptor blockade and when donor hearts were from reserpine-pretreated guinea pigs. In was concluded that pacing released endogenous catecholamines which in turn released the vasodilator material. Pacing per se did not cause vasodilatation or release of the vasodilator. The [Formula: see text] of perfusates from donor hearts was reduced by pacing at 5 Hz (25.7 ± 5.2 mmHg) and by isoproterenol (10 ng, 32.0 ± 3.7 mmHg), indicative of an elevated oxygen extraction. The isoproterenol-induced falls in [Formula: see text] were abolished by β-adrenoceptor blockade. However, the pacing-induced falls in [Formula: see text] persisted, the values occurring before (25.7 ± 5.2 mmHg) and after propranolol (45.7 ± 4.5 mmHg) and before (32.1 ± 1.1 mmHg) and after practolol (27.3 ± 4.1 mmHg) not differing significantly (p > 0.05). These falls in perfusate [Formula: see text] were not accompanied by coronary vasodilatation or release of vasoactive material. Perfusate [Formula: see text] changes could therefore be dissociated from the coronary vasodilatation and vasoactive material release, suggesting that hypoxia may not be a prerequisite for the metabolic autoregulatory vasodilatation in response to myocardial hyperactivity induced by cardiac stimulants.
Platelet antiaggregatory substances inhibit arachidonic acid induced coronary constriction
Authors: Ioannou Petros , Talesnik Jaime
Published: April 2011

Isolated perfused hearts of rats and guinea pigs reacted to arachidonic acid (AA) with coronary vasoconstriction followed by vasodilatation. The infusion of prostacyclin (PGI2), Iloprost, hydralazine (HYD), and nifedipine (NFP) elicited a vasodilatation that nullified the coronary flow reserve, therefore the AA-induced vasodilatation was abolished. Dipyridamole (DPY) and 1-methyl-3-isobutylxanthine (MIX) produced a slight coronary dilatation without restricting the dilatation induced by AA. Regardless of their vasodilator action, all these drugs acted by inhibiting the AA-induced coronary constriction, while their infusion lasted. We postulated that a thromboxane-like substance, formed from AA in the vascular walls, would be responsible for the coronary vasoconstriction caused by AA. The inhibition of the AA-induced coronary constriction by PGI2, Iloprost, HYD, NFP, DPY, and MIX may be explained by an inhibitory action of these drugs on the synthetic processes of the thromboxane-like substance.
Segmental projection from muscle spindles: a perspective from the upper cervical spinal cord
Authors: Rose P. K. , Keirstead S. A.
Published: April 2011

The segmental connections of muscle spindle afferents originating from primary endings do not follow the same pattern at all levels of the spinal cord. This review is concerned with the characteristics of neck muscle spindle projections, which illustrate several differences between their segmental organization and the arrangement of hindlimb muscle spindle afferents in the lumbosacral spinal cord.