bluuebunny/crossref_metadata_2025 huggingface dataset:
Antagonists of epithelial chloride channels inhibit cAMP synthesis
Authors: Heisler S.
Published: April 2011

In past studies we observed that the chloride channel blocker, diphenylamine-2-carboxylate (DPC) and chemically related drugs (Hoechst compounds 131, 143, 144) inhibited cAMP formation in mouse pituitary tumor cells. The object of this study was to determine whether these drugs inhibited chloride transport in human T-84 colonic carcinoma cells through an effect on cAMP metabolism. Chloride secretion (measured as 125I efflux from isotope-preloaded cells) was stimulated in a concentration-dependent manner by vasoactive intestinal polypeptide (VIP) (EC50 = 1.5 × 10−10 M) which similarly increased cAMP synthesis (EC50 = 1.6 × 10−8 M). The cAMP response to VIP was inhibited 17, 52, 55, and 78% maximally by DPC and compounds 144, 143, and 131, respectively. In untreated T-84 cells, 125I secretion fell by 66% after 3 min; VIP (10−7 M) increased secretion about fivefold over the same period. Both basal and VIP-stimulated 125I secretion were inhibited up to 60% by compound 131. Pretreatment of cells with pertussis toxin did not attenuate the inhibitory effect of channel blockers on either VIP-stimulated cAMP synthesis or 125I secretion. The cationophore, A-23187, which had no effect on cAMP formation, and 8-Br-cAMP both stimulated 125I secretion from T-84 cells. These secretory responses were inhibited by compound 131. The mechanism by which phenylanthranilic acids antagonize cAMP synthesis and its significance is not known; however, the data suggest that this family of drugs may inhibit chloride transport by both cAMP-dependent and independent mechanisms.Key words: T-84 cells, chloride secretion, vasoactive intestinal polypeptide, diphenylamine-2-carboxylate, inhibition of cyclic AMP synthesis.
Sympathoadrenal system in neuroendocrine control of glucose; mechanisms involved in the liver, pancreas, and adrenal gland under hemorrhagic and hypoglycemic stress
Authors: Yamaguchi Nobuharu
Published: April 2011

Glucose homeostasis is maintained by complex neuroendocrine control mechanisms, involving three peripheral organs: the liver, pancreas, and adrenal gland, all of which are under control of the autonomic nervous system. During the past decade, abundant results from various studies on neuroendocrine control of glucose have been accumulated. The principal objective of this review is to provide overviews of basic adrenergic mechanisms closely related to glucose control in the three peripheral organs, and then to discuss the integrated glucoregulatory mechanisms in hemorrhage-induced hypotension and insulin-induced hypoglycemia with special reference to sympathoadrenal control mechanisms. The liver is richly innervated by sympathetic and parasympathetic nerves. The functional implication in glucoregulation of sympathetic nerves has been well-documented, while that of parasympathetic nerves remains less understood. More recently, hepatic glucoreceptors have been postulated to be coupled with capsaicin-sensitive afferent nerves, conveying sensory signals of blood glucose concentration to the central nervous system. The pancreas is also richly supplied by the autonomic nervous system. Besides the well documented adrenergic and cholinergic mechanisms, the potential implication of peptidergic neurotransmission by neuropeptide Y and neuromodulation by galanin has recently been postulated in the endocrine secretory function. Presynaptic interactions of these putative peptidergic neurotransmitters with the classic transmitters, noradrenaline and acetylcholine, in the pancreas remain to be clarified. It may be of particular interest that it was vagus nerve stimulation that caused a dominant release of neuropeptide Y over that caused by sympathetic nerve stimulation in the pig pancreas. The adrenal medulla receives its main nerve supply from the greater and lesser splanchnic nerves. Adrenal medullary catecholamine secretion appears to be regulated by three distinct local mechanisms: adrenoceptor-mediated, dihydropyridine-sensitive Ca2+ channel-mediated, and capsaicin-sensitive sensory nerve-mediated mechanisms. In response to hemorrhagic hypotension and insulin-induced hypoglycemia, the sympathoadrenal system is activated resulting in increases of adrenal catecholamine and pancreatic glucagon secretions, both of which are significantly implicated in glucoregulatory mechanisms. An increase in sympathetic nerve activity occurs in the liver during hemorrhagic hypotension and is also likely to occur in the pancreas in response to insulin-induced hypoglycemia. The functional implication of hepatic and central glucoreceptors has been suggested in the increased secretion of glucose counterregulatory hormones, particularly catecholamines and glucagon.Key words: sympathetic nerves, adrenal medulla, catecholamines, glucose, hypoglycemia, hemorrhage.
Channels activated by stretch in neurons of a helix snail
Authors: Bédard Elaine , Morris Catherine E.
Published: April 2011

Single-channel recordings from central neurons of the helix snail, Cepaea nemoralis, revealed two types of channels that could be activated by stretch (i.e., by the membrane deformation produced when suction is applied to the patch pipette). One, a K+ channel (58 pS in physiological solution), was evident in excised and cell-attached patches. Its conductance in symmetrical [K+] solutions indicated a channel of high K+ permeability (PK = 3.4 × 10−13 cm/s). Though osmoregulation has been suggested as a function for such channels, comparisons among molluscs indicate osmotic milieu does not govern their expression; Cepaea is terrestrial, and stretch-activated K+ channels similar to those described here occur in aquatic and marine molluscs. The second type of channel, observed only in excised patches, was Cl− permeant; it had a large conductance (130 pS) and was inactive prior to patch excision. Membrane tension may not be the physiological activator of either the K+ or Cl− channel; the channels are designated as stretch-activated channels on the basis of their experimental behaviour during single-channel recording.Key words: K+ channel, Cl− channel, snail neuron, stretch activation.
Partial inhibition of skeletal muscle contraction by dantrolene sodium and its modification with perchlorate and Bay K 8644
Authors: Oba Toshiharu , Aoki Takako , Lu Aiping , Yamaguchi Mamoru
Published: April 2011

The effects of dantrolene sodium (DAN) on the dihydropyridine receptor (DHPR) of the transverse (T) tubule voltage sensor (Ca2+ channel) was studied with single fibers from bullfrog toe muscle. Perchlorate [Formula: see text], which acts selectively on the DHPR, overcame DAN-induced inhibition of twitch tension. Bay K 8644, a DHPR agonist, slowed the rate of twitch inhibition by DAN. DAN inhibited twitch tension to a greater extent in Ca2+-free solution than in Ringer solution or solution containing Zn2+, whereas twitch inhibition by DAN was less in caffeine-containing solution than in the control. The effects of DAN on Zn2+- and caffeine-treated fibers and on fibers in Ca2+-free solution suggest that DAN must act near the voltage sensor of the T tubule. However, differences in net twitch inhibition by DAN between control fibers and fibers potentiated by [Formula: see text] or Bay K 8644 suggest that DAN does not bind to the same site as these potentiating agents do. The role of myoplasmic Ca2+ in DAN-induced inhibition of twitch and the effects of DAN on the mechanical threshold and membrane potential in skeletal muscle are discussed.Key words: dantrolene sodium, perchlorate, Bay K 8644, twitch tension.
Nonselective cation channels in intact human T lymphocytes
Authors: Schlichter L. C.
Published: April 2011

Nonselective cation channels were found in single channel recordings from cell-attached patches on human T lymphocytes. These channels were active under conditions that should lead to cell swelling (hypotonic bath solutions with NaCl or KCl); however, a definite dependence of activity on cell swelling has not been proven. Under these conditions similar channels were found in 20 of 23 patches from 11 different blood donors. The current–voltage relation was approximately linear for outward current (11–14 pS) and inwardly rectifying (to 23 pS) when the intact cells were depolarized with high KCl in the bath. The voltage dependence of channel activity is consistent with closing at hyperpolarized membrane potentials (Vm ≤ −50 mV) and block of open channels at strongly depolarized membrane potentials (Vm > 0 mV). Reversal potentials under all ionic gradients tested are consistent with a channel that is poorly selective between Na+ and K+ ions. Active channels in cell-attached patches were rapidly blocked by bath addition of the membrane-permeant inhibitor quinine. Channels that were active in cell-attached became quiescent after patch excision; however, two patches remained active long enough to obtain current–voltage relations. These were linear with a slope conductance for outward current of 8–11 pS. Because of the clustering of single-channel openings, detailed voltage dependence of kinetics and probability of opening were not studied.Key words: lymphocytes, volume regulation, cation channels, patch clamp, human T cells.
Direct evidence for nitric oxide formation from glyceryl trinitrate during incubation with intact bovine pulmonary artery
Authors: Marks Gerald S. , McLaughlin Brian E. , Nakatsu Kanji , Brien James F.
Published: April 2011

It has been proposed that the mechanism of the vasodilator action of glyceryl trinitrate (GTN) involves biotransformation to nitric oxide. A sensitive chemiluminescence method for nitric oxide determination was used to test this hypothesis. In four experiments, bovine pulmonary artery (BPA) was incubated with GTN (0.1 mM) in Krebs' solution (2 mL) containing 30 mM KCl, and in anaerobic conditions using 95% Ar – 5% CO2, in a sealed micro-Fernbach flask (6.2-mL volume). After incubation for 2, 5, 10, or 20 min at 37 °C, 400-μL aliquots of headspace gas were removed and injected into a redox chemiluminescence detector. Nitric oxide formation was first measurable at 5 min (76 ± 53 pmol/g wet wt. BPA), and increased with incubation time (174 ± 46 pmol/g wet wt. BPA after 10 min and 310 ± 67 pmol/g wet wt. BPA after 20 min). This is the first direct chemical measurement of nitric oxide formation during interaction of GTN with vascular smooth muscle. These data support the concept that GTN is a nitrovasodilator prodrug acting via the formation of nitric oxide.Key words: nitric oxide formation, glyceryl trinitrate, chemiluminescence, bovine pulmonary artery, vasodilation.
ATP-MgCl2 restores renal microcirculation following trauma and severe hemorrhage
Authors: Wang Ping , Zhou Mian , Rana M. Waheed , Singh Gurdev , Ba Zheng F. , Ayala Alfred , Chaudry Irshad H.
Published: April 2011

Although ATP-MgCl2 enhances the recovery of renal function after ischemia and reperfusion, it is not known whether this agent has any beneficial effects on renal microcirculation and function in a nonheparinized model of trauma and severe hemorrhage. To study this, a midline laparotomy was performed (i.e., trauma induced) and the rats were bled to and maintained at a mean arterial pressure of 40 mmHg (1 mmHg = 133.32 Pa) until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL) solution. Animals were then resuscitated with 4 times the volume of the shed blood in the form of RL. ATP-MgCl2, 50 μmol/kg body weight, or an equivalent volume of saline, was infused intravenously during and following resuscitation. Renal microcirculation was examined by using colloidal carbon infusion and laser Doppler flowmetry. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance and cardiac output (CO) was determined by dye dilution technique. The results indicate that the depressed renal microcirculation following hemorrhage and resuscitation was restored by ATP-MgCl2 treatment. GFR was significantly higher in ATP-MgCl2-treated than saline-treated rats. ATP-MgCl2 also increased urine output, restored the decreased CO, and prevented the occurrence of renal edema after hemorrhage and resuscitation. Thus, ATP-MgCl2 appears to be a useful adjunct to crystalloid resuscitation following trauma and severe hemorrhagic shock even in the absence of blood resuscitation.Key words: adenosine triphosphate effects, cardiac output, colloidal carbon perfusion, glomerular filtration rate, laser Doppler flowmetry.
Acute exposure to human interferon-α affects ion currents in human natural killer cells
Authors: Schlichter L. C.
Published: April 2011

Interferon-α (IFN-α) is a particularly potent stimulator of human natural killer (NK) cell activity. The initial trigger for IFN action is not known, but there is indirect evidence from a number of cell types that changes in ion channel activity are among the earliest responses. Previous evidence includes changes in Ca2+ fluxes and intracellular activity, membrane potential changes, and effects of ion-channel blockers. Killing by human NK cells is dependent on external Ca2+ and on K+ channel activity. In the present study we have confirmed this dependence and the augmentation by human IFN-α. Then we directly studied the effects of IFN-α on ion currents in human NK cells using the patch-clamp electrophysiological techniques. We find that IFN-α can increase the predominant K+ current near the resting potential but suppresses it at higher voltages. Within 1 min after acute IFN-α treatment a new current is induced. This small current appears to be through nonselective cation channels that allow monovalent and divalent cations, including Ca2+ to permeate. This current presents a possible early triggering mechanism whereby acute exposure to IFN-α augments NK cytotoxicity.Key words: natural killer cell, interferon, K+ channel, cation channel, calcium, natural killer augmentation.
M2 muscarinic ([3H]N-methyl scopolamine) binding in micropunches of rat ventricular myocardium: characterization and modification by progesterone
Authors: Wilkinson M. , Giles Alice , Wilkinson Diane A.
Published: April 2011

A new technique is outlined for the characterization and quantification of M2 muscarinic binding sites (receptors) in micro-punches (1 mm diam.), cut from slices (350 μm), of fresh cardiac tissue using the hydrophilic antagonist [3H]N-methyl scopolamine. The use of this water-soluble ligand allows us to label, and quantify, M2 receptors on the cell surface of intact cells contained within the micropunch. We believe that cardiac micropunches offer a simple but powerful approach to the investigation of membrane receptor regulation in tissue that largely retains the in vivo cytoarchitecture. Specific binding is reversible, stereospecific, saturable, of high affinity, and has the drug specificity typical of an M2 muscarinic receptor. In rat left ventricle, Bmax was 151.2 ± 10.3 fmol/mg protein while KD was 1.0 ± 0.1 nM. Nonspecific binding of the ligand was very low, varying from 2.8% (at 0.27 nM) to 7.7% (at 3.58 nM). This micropunch assay was used to determine that progesterone can compete with the muscarinic ligand for the M2 receptor in vitro (IC50 = 50 × 10−6 M). The steroids estradiol and testosterone, as well as ouabain, were without effect. Progesterone inhibited [3H]N-methyl scopolamine binding competitively (KD reduced from 1.9 to 4.3 nM) without affecting the rate of association of the ligand. However, progesterone induced a rapid dissociation of the ligand from its receptor. We conclude that the micropunch assay described here is suitable for the continued study of sex hormone effects on cardiac function.Key words: cardiac micropunches, muscarinic receptor, progesterone, [3H]N-methyl scopolamine.
Intrafibre distribution of succinate dehydrogenase in cat tibialis anterior motor units
Authors: Martin Thomas P. , Edgerton V. R.
Published: April 2011

Using isolated ventral root filament stimulation and glycogen depletion techniques, 14 motor units from the cat tibialis anterior were studied. Based on their mechanical properties, the units were classified as either slow-fatigue resistant, fast-fatigue resistant, fast-fatigue intermediate, or fast-fatigable. Quantitative histochemical and computer assisted image analysis techniques were used to determine the activity of succinate dehydrogenase in a population of fibres in each unit. In addition, the intrafibre distribution of succinate dehydrogenase activity was measured in those same fibres by calculating the enzymatic activity of circumferential layers every 0.5 μm starting from the fibre edge to its centre. It was established that enzymatic activity and radial distance were linearly related in the fibres. A range in succinate dehydrogenase activity (mean coefficient of variation, 29%) was observed among the fibres of a unit. In contrast, the intrafibre distribution of that activity was rather consistent (mean variation, 4%) across the fibres of a unit. Further, the intrafibre distribution was similar among the fibres of units classified as the same type. However, the intrafibre distribution was disparate among the different unit types. These data suggest that the intrafibre distribution of mitochondrial enzymes may contribute to the mechanical properties of a motor unit. In this regard, a hypothesis is proposed that describes how the absolute activity of a mitochondrial enzyme, and the intrafibre distribution of that activity, may interactively contribute to the fatigue resistance of a unit.Key words: mitochondria, quantitative histochemistry, fatigue.
Reversibility of renal tubular dysfunction in streptozotocin-induced diabetes in the rat
Authors: Chouinard S. , Viau C.
Published: April 2011

Enzymuria and specific proteinuria were examined over a period of 19 days in 4 groups of 5 rats: a control group, a non-diabetic polyuric group, a group of streptozotocin-induced diabetic rats treated with insulin as of the 10th day after the injection of the drug, and a similar group of untreated diabetic rats. Increased urinary excretion of β-N-acetyl-D-glucosaminidase, lactate dehydrogenase, and alanine aminopeptidase was observed shortly after the induction of diabetes. It was partly or totally reversible following insulin treatment. Nondiabetic polyuria had a slight effect on the excretion of alanine aminopeptidase only. The urinary excretion of β2-microglobulin also rapidly increased after the onset of diabetes to a level approximately 50 times the control values. This effect was largely reversible with insulin treatment and was absent in the nondiabetic polyuric group. A small but significant 3-fold increase in albumin excretion was also noted but was not affected by insulin treatment. We conclude that streptozotocin-induced diabetes causes an early tubular dysfunction that is unrelated to polyuria and is reversible upon insulin treatment. This tubular dysfunction is best revealed by the urinary excretion of the low molecular weight protein β2-microglobulin. Our results suggest that it would be of interest to further examine the usefulness of sensitive markers of tubular dysfunction, especially low molecular weight proteinuria, in the detection of early stages of diabetic nephropathy.Key words: diabetic nephropathy, enzyme, urine, proteinuria, β2-microglobulin, streptozotocin, insulin, rat.
Regional venous outflow, blood volume, and sympathetic nerve activity during hypercapnia and hypoxic hypercapnia
Authors: Hoka Sumio , Arimura Hiroyuki , Bosnjak Zeljko J. , Kampine John P.
Published: April 2011

We examined the changes in systemic blood volume and regional venous outflow from the splanchnic, coronary, and other remaining vascular beds in response to acute hypercapnia or hypoxic hypercapnia in dogs, using cardiopulmonary bypass and a reservoir. Hypercapnia [Formula: see text] (1 mmHg = 133 Pa) and hypoxic hypercapnia ([Formula: see text], [Formula: see text]) caused marked decreases in systemic blood volume of 14 ± 3 and 16 ± 3 mL/kg in spleen-intact dogs, and 3 ± 2 and 10 ± 2 mL/kg in splenectomized dogs, respectively. Splanchnic venous outflow increased by 12% at 3.5 min hypercapnia, whereas it decreased by 60% at 3.5 min hypoxic hypercapnia. Coronary venous outflow increased by 85 and 400% at 3.5 min hypercapnia and hypoxic hypercapnia, respectively. Sympathetic efferent nerve activity revealed a significant augmentation during hypoxic hypercapnia and a relatively smaller increase (30% of the response to hypoxic hypercapnia) during hypercapnia. Carotid and aortic chemoreceptor and baroreceptor denervation attenuated significantly the response of systemic blood volume to hypercapnia and hypoxic hypercapnia. The regional venous outflow responses to hypercapnia were not altered after chemodenervation, but those to hypoxic hypercapnia were significantly attenuated after chemodenervation. These results suggest that acute hypercapnia and hypoxic hypercapnia caused a marked decrease in vascular capacitance owing primarily to an increase in sympathetic efferent nerve activity via chemoreceptor stimulation. They also indicate that blood flow to the splanchnic vascular bed during hypercapnia increased (even though the cardiac output was constant), whereas it increased to the extrasplanchnic and coronary vascular beds during hypoxic hypercapnia.Key words: blood flow distribution, hypercapnia, hypoxia, vascular capacitance, splanchnic blood volume.
Role of the sympathetic nervous system in the alcohol–guanabenz hemodynamic interaction
Authors: Abdel-Rahman Abdel A. , Carroll Robert G. , El-Mas Mahmoud M.
Published: April 2011

The present study evaluated the contribution of the sympathetic nervous system to the adverse hemodynamic action of ethanol on hypotensive responses in conscious unrestrained spontaneously hypertensive rats. Ethanol caused a dose-related attenuation of the hypotensive effect of guanabenz. An equivalent hypotensive response to sodium nitroprusside was not influenced by ethanol, which indicates a potential specific interaction between ethanol and guanabenz. Alternatively, it is possible that a preexisting high sympathetic nervous system activity, which occurred during nitroprusside infusion, may mask a sympathoexcitatory action of ethanol. Further, ethanol (1 g/kg) failed to reverse the hypotensive effect of the ganglionic blocker hexamethonium. This suggests that a centrally mediated sympathoexcitatory action of ethanol is involved, at least partly, in the reversal of hypotension. In addition, the antagonistic interaction between ethanol and guanabenz seems to take place within the central nervous system and involves opposite effects on central sympathetic tone. Finally, changes in plasma catecholamines provide supportive evidence for the involvement of the sympathetic nervous system in this interaction. In a separate group of conscious spontaneously hypertensive rats, ethanol (1 g/kg) reversed the guanabenz-evoked decreases in blood pressure and plasma catecholamine levels. It is concluded that (i) ethanol adversely interacts with centrally acting antihypertensive drugs through a mechanism that involves a directionally opposite effect on sympathetic activity, and (ii) a sympathetically mediated pressor effect of ethanol is enhanced in the presence of an inhibited central sympathetic tone.Key words: spontaneously hypertensive rats, ethanol, catecholamines, guanabenz, hexamethonium.
Abnormal magnesium metabolism in two rat models of genetic hypertension
Authors: Wells I. C. , Agrawal D. K.
Published: April 2011

Magnesium concentrations in erythrocyte ghosts and arterial tissue of male, spontaneously hypertensive rats (SHR) were significantly less than in these tissues of male normotensive controls (Wistar–Kyoto; WKY) of the same age, which were also fed rat chow and tap water. The magnesium concentration in SHR erythrocyte ghosts was increased to the control value by incubating SHR erythrocytes with WKY blood plasma; SHR plasma did not affect the magnesium concentration in WKY erythrocyte ghosts. The magnesium concentrations in erythrocyte ghosts, aortas, and mesenteric arteries from female salt-sensitive (SS/JR) and salt-resistant (SR/JR) Dahl-derived rats, both maintained ad libitum on laboratory rat chow and either tap water or 0.9% NaCl, were not different but were significantly less than those of Sprague–Dawley rats considered as controls. While the ingestion of 0.9% NaCl had no effect on the magnesium concentrations measured in these animals, it caused the salt-sensitive rats to become severely hypertensive. It is evident from these observations that the decreased binding of magnesium to the plasma membrane of cells may be an inheritable metabolic defect that may be associated with the development of hypertension. However, in those instances of hypertension in which this defect occurs, it appears to be a contributing cause of the hypertension; by itself the defect is not a cause of hypertension.Key words: essential hypertension, magnesium, SHR rats, salt-sensitive rats (SS/JR).
Brush border membrane proteins in experimental Fanconi's syndrome induced by 4-pentenoate and maleate
Authors: Pouliot Jean-François , Gougoux André , Béliveau Richard
Published: April 2011

Fanconi's syndrome was investigated using brush border membrane (BBM) vesicles isolated from dog kidney. Sodium-dependent uptake of glucose, phosphate, and amino acids and protein phosphorylation were studied in BBM isolated from normal and from 4-pentenoate- and maleate-treated animals. The time course of D-glucose and phosphate uptake, in BBM vesicles, remained unchanged, indicating that both treatments had no effect on carrier properties, and that permeabilities to these substrates and to sodium were not modified. Furthermore, sodium-dependent transport of alanine, phenylalanine, proline, glycine, and glutamate into vesicles remained unaltered by either treatment. 4-Pentenoate treatment caused modifications of the phosphorylation pattern of BBM proteins: the phosphorylation of two proteins (61 and 74 kDa) was increased and that of two others (48 and 53 kDa) was decreased. Maleate treatment caused an increase in the phosphorylation for the same 61-kDa protein, which was also affected by 4-pentenoate treatment, suggesting that phosphorylation of this protein could be related to a mechanism involved in both 4-pententoate- and maleate-induced Fanconi's syndrome. These changes were also observed in the presence of sodium fluoride and L-bromotetramisole, indicating that the modification of phosphorylation was not due to a difference in phosphatase activities. These results suggest that Fanconi's syndrome induced by 4-pentenoate or maleate is not caused by an inhibition of BBM Na+-dependent transport systems. Our results also suggest that protein phosphorylation may play an important role in the molecular defect involved in Fanconi's syndrome.Key words: Fanconi's syndrome, 4-pentenoate, maleate, transport, phosphorylation.
Effect of training and detraining on skeletal muscle glucose transporter (GLUT4) content in rats
Authors: Neufer P. D. , Shinebarger M. H. , Dohm G. L.
Published: April 2011

The aim of the present study was to examine the effects of treadmill exercise training and detraining on the skeletal muscle fiber type specific expression of the insulin-regulated glucose transporter protein (GLUT4) in rats. GLUT4 protein content was determined by Western and dot-blot analysis, using a polyclonal antibody raised against the carboxy-terminal peptide. Rats were sacrificed 24 h after the last training session. There were no significant changes in muscle GLUT4 after 1 day or 1 week of training. Six weeks of training increased GLUT4 protein content 1.4- to 1.7-fold (p < 0.05) over controls in the soleus and red vastus lateralis, whereas no significant change was evident in the white vastus lateralis muscle. GLUT4 protein content in both soleus and red vastus lateralis muscle returned to near control values after 7 days of detraining. Similar to GLUT4, citrate synthase activity showed no change after 1 day or 1 week of training, increased 1.8-fold over controls after 6 weeks of training, but returned to control values after 7 days detraining. These findings demonstrate that muscle GLUT4 protein is increased in rats with as little as 6 weeks of treadmill exercise training but that the adaptation is lost within 1 week of detraining. It is suggested that expression of the GLUT4 protein is coordinated with the well-documented adaptations in oxidative enzyme activity with endurance training and detraining.Key words: insulin-regulated glucose transporter protein, citrate synthase.
An AF-DX 116 sensitive inhibitory mechanism modulates nicotinic and muscarinic transmission in cat superior cervical ganglion in the presence of anticholinesterase
Authors: Bachoo M. , Polosa C.
Published: April 2011

The effect of the muscarinic receptor antagonist AF-DX 116 on the inhibitory action of muscarinic agonists and on responses mediated by nicotinic or muscarinic ganglionic transmission was studied in the superior cervical ganglion of the anesthetized cat. The postganglionic compound action potential evoked by cervical sympathetic trunk stimulation was depressed by methacholine or acetylcholine (ACh) injected into the ganglionic arterial supply. The depression was blocked by AF-DX 116. The compound action potentials evoked by preganglionic stimulus trains were also depressed when the intratrain frequency was 2 Hz or greater. This intratrain depression was, however, insensitive to AF-DX 116. The anticholinesterase drug physostigmine markedly enhanced the intratrain depression of the compound action potential. This effect was reversed by AF-DX 116. During nicotinic receptor block with hexamethonium, preganglionic stimulus trains with intratrain frequencies of 5 Hz or greater produced nictitating membrane contractions that could be blocked by the M1 muscarinic receptor antagonist pirenzepine. The amplitude of the contractions increased with frequency and reached a maximum at 20–40 Hz. AF-DX 116 had no effect on these responses. After administration of physostigmine, the amplitude of the nictitating membrane responses decreased with increasing intratrain frequency. AF-DX 116 reversed this effect. The data suggest that, in the superior cervical ganglion, AF-DX 116 sensitive muscarinic receptors which depress synaptic transmission are activated by exogenous agonists but not by the ACh released by the preganglionic axon terminals unless cholinesterase activity is inhibited. This may result from the fact that these receptors, although accessible to agonists injected into the ganglionic arterial supply, are remote from synaptic release sites and that, under normal conditions, cholinesterase activity prevents sufficient activation of these receptors by the nerve-released ACh to result in modulation of synaptic transmission.Key words: muscarinic inhibition, M2 receptors, sympathetic ganglion modulation.
Modification of the renal response to endopeptidase inhibition and atrial natriuretic peptide infusion in normal dogs
Authors: Levy Mortimer , Cernacek Peter
Published: April 2011

Inhibition of intrarenal neutral endopeptidase 24:11 (NEP) increases the natriuretic response to infused atrial natriuretic peptide (ANP). In various models of canine heart failure, angiotensin and kinins have been shown to modulate ANP and (or) NEP activity. In the present study, we examined possible modulators of NEP activity in normal dogs by infusing various agents into the left renal artery (or by denervating the left kidney) and comparing the response of this kidney with that of the contralateral one following the combined intravenous infusion of Squibb 28603 (a potent NEP inhibitor) and ANP (75 ng∙kg−1∙min−1). Four dogs received angiotensin (1.5 ng∙kg−1∙min−1) into the left renal artery, 8 dogs received saralasin (5 μg/min), 5 dogs received noradrenaline (2 μg/min), and 6 dogs received bradykinin (3 μg/min). Five dogs underwent left renal denervation. Angiotensin inhibited sodium excretion following the NEP inhibitor alone and after the NEP inhibitor plus ANP. Saralasin augmented the natriuretic response. None of the other protocols influenced sodium excretion. We conclude that angiotensin may modulate either the enzymatic degradation of ANP or influence its renal tubular effects.Key words: angiotensin, sodium excretion, kinins, neutral endopeptidase.
Serotonin (5-HT2) receptor mediated enhancement of cortical unit activity
Authors: Neuman R. S. , Zebrowska G.
Published: April 2011

Simultaneous single-unit and intracortical activity were recorded from neocortical neurons in urethane-anaesthetized rats to investigate the role of serotonin (5-HT) in modifying cortical excitability. Units, at a depth of 775–1100 μm from the pial surface, discharged in a burst–pause pattern that was correlated with slow wave activity. Application of noxious somatic stimulation resulted in cortical desynchronization and altered the pattern of unit activity such that firing was continuous, i.e., the pauses were eliminated. Intravenous administration of the mixed 5-HT1C/5-HT2 antagonists (cinanserin, cyproheptadine, ketanserin, and ritanserin) prevented both desynchronization and the change in unit activity induced by noxious stimulation within 2.5–15 min of the injection. The basic pattern of burst–pause activity remained intact, but the number of spikes per burst was typically reduced, whereas interburst intervals were increased. Iontophoretic application of these antagonists onto cortical neurons resulted in actions similar to those observed following systemic administration. Intravenous and iontophoretic application of m-trifluomethylphenylpiperazine (5-HT1C agonist, 5-HT2 antagonist) resulted in actions indistinguishable from those observed with the above antagonists, from which we conclude 5-HT2 and not 5-HT1C receptors mediate the alteration in unit activity observed with noxious stimulation. The results are discussed with respect to an interaction between N-methyl-D-aspartate and 5-HT2 receptors leading to the enhanced unit activity observed with noxious stimulation.Key words: neocortex, serotonin antagonists, unit activity, noxious stimulation, desynchronization.
5-(N-Ethyl-N-isopropyl)amiloride sensitive Na+ currents in intact fetal distal lung epithelial cells
Authors: Wang X. , Kleyman T. R. , Tohda H. , Marunaka Y. , O'Brodovich H.
Published: April 2011

To determine whether primary cultures of rat fetal distal lung epithelium (FDLE) possessed L-type Na+ channels on their plasma membrane we performed experiments with 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and other amiloride analogs. Short-circuit current (Isc) was decreased by the apical application of amiloride and benzamil, but was unaffected by 10 μM dimethylamiloride (DMA). EIPA decreased Isc when added to either the apical or basal sides. Greatest effects were seen with bilateral EIPA, where half-maximal effects occurred in the micromolar range. Measurements of intracellular pH with the fluorescent dye BCECF demonstrated that DMA impaired (IC50 = 71 nM) the ability of FDLE to recover from intracellular acidification. Nystatin perforated patch clamp techniques snowed that FDLE had nonrectifying Na+ currents but no detectable Cl− currents. The whole-cell currents were reversibly decreased by 20 μM concentrations of EIPA, benzamil, and amiloride but were unaffected by 20 μM DMA. These studies indicate that there are EIPA-sensitive Na+ conductances in intact FDLE and suggest the presence of L-type Na+ conductances on their apical membrane and EIPA-sensitive K+ channels on the basolateral membrane.Key words: Na+ channels, 5-(N-ethyl-N-isopropyl)amiloride, alveolar epithelium, whole-cell patch clamp, K+ channels.
Leukocyte – endothelial cell adhesion induced by ischemia and reperfusion
Authors: Granger D. Neil , Kvietys Peter R. , Perry Michael A.
Published: April 2011

Reperfusion of ischemic tissues is associated with an enhanced production of inflammatory mediators, increased rolling, adherence, and emigration of leukocytes in postcapillary venules, and vascular protein leakage. There is a growing body of evidence that the leukocyte – endothelial cell interactions are largely responsible for the microvascular dysfunction induced by ischemia–reperfusion. Oxygen radicals, produced by xanthine oxidase and other enzymes, appear to play an important role in initiating and amplifying the inflammatory response elicited by ischemia–reperfusion, while neutrophilic proteases contribute significantly to the injury response. The magnitude of the inflammatory responses observed during ischemia and reperfusion is also influenced by adhesion forces generated by specific glycoproteins expressed on the surface of granulocytes and microvascular endothelium, as well as shear forces that are generated by the movement of blood within the microcirculation. Manipulation of free-radical production, leukocyte – endothelial cell adhesion, and (or) intravascular shear forces provides an effective means for attenuating the deleterious influences of ischemia–reperfusion on the microvasculature.Key words: leukocyte integrins, microvascular injury, oxygen free radicals, xanthine oxidase, platelet-activating factor.
Relative rates of appearance of nitrogen and sulphur: implications for postprandial synthesis of proteins
Authors: Cheema-Dhadli Surinder , Halperin Mitchell L.
Published: April 2011

The purpose of this study was to gain insights on the temporal fate of proteins based on the rate of appearance of waste products of nitrogen (urea) and sulphur (sulphate) metabolism. Urine was collected every 2 h from 25 normal subjects to measure the rates of excretion of urea, creatinine, and sulphate throughout the 24-h cycle. Samples of blood and urine were also obtained over a 4-h period from 10 subjects who consumed a mixed meal containing 0.4 g protein/kg body weight to obtain information on the relative rates of degradation of amino acids with and without sulphur in a noninvasive fashion. The daily excretion (mean ± SEM) of urea, creatinine, and sulphate was 396 ± 28, 14 ± 0.4, and 15 ± 0.6 mmol, respectively; the molar sulphate/nitrogen (S/N) ratio was 2.0 ± 0.1%. There were relatively minor (<20%) excursions in the rate of excretion of urea and creatinine in any 2-h period as compared with the corresponding 24-h rate; the concentrations of urea and creatinine in plasma also varied <20% throughout the day. Only 23% of the nitrogen in protein in the standard meal appeared as urea in the 210 min after this meal was consumed. The small changes in the rate of appearance of urea and creatinine imply that the oxidation of amino acids was spread out over the day. In contrast to urea and creatinine, the rate of appearance of sulphate underwent a greater variation; in general, there was a nadir just after breakfast and a peak overnight (7.0 ± 0.6 and 14.3 ± 1.6 μmol/min, respectively), and a S/N appearance rate that rose from 1.3 to 2.6%, suggesting specific retention of sulphur-containing compounds during the day, with catabolism occurring many hours later. When there was a low intake of protein for 40 h, the S/N appearance rate changed appreciably: the mean value fell in the last 24 h from 1.8 ± 0.1 to 1.2 ± 0.1% when carbohydrate was consumed, whereas it was 2.3 ± 0.1% during a 40-h fast. We conclude that most of the amino acids of dietary origin are not catabolized directly after a meal in normal subjects and that sulphur in proteins or other compounds is retained for longer periods following meals. During a 40-h fast, net protein catabolism includes proteins rich in of sulphur-containing amino acids, whereas the converse occurs when subjects consumed the low protein – high carbohydrate diet.Key words: amino acids, creatinine, diurnal variation, nitrogen balance, protein turnover, sulphate, urea.
Cardiac output and left ventricular function in response to exercise in older men
Authors: Thomas Scott G. , Paterson Donald H. , Cunningham David A. , McLellan Douglas G. , Kostuk William J.
Published: April 2011

Studies of the cardiovascular response to exercise in older subjects have presented conflicting data regarding left ventricular function, the cardiac output – oxygen consumption [Formula: see text] relationship, and the pattern of change in [Formula: see text], stroke volume (SV), and arteriovenous O2 difference. We have examined the cardiovascular response to submaximal and strenuous exercise in 96 men of mean age 63 years during an incremental treadmill test with [Formula: see text] determined by CO2 rebreathing, and in 12 subjects studied during incremental supine exercise with left ventricular volumes evaluated by radionuclide angiocardiography. During treadmill exercise the [Formula: see text] was approximately 10% lower than reported for younger samples, with a lower intercept of the [Formula: see text] relationship. During near-maximal exercise [Formula: see text] was approximately 15 L∙min−1, with SV of 95 mL plateauing or showing a small decline in heavy work. Peak arteriovenous O2 difference (150+ mL∙L−1) approached values of the young. During the supine exercise SV increased from rest to exercise, with a consistent increase in ejection fraction (rest, 66%, to peak exercise, 76%). In contrast to a prior report, the end-diastolic volume was constant, with the increase of SV attributable to a reduced end-systolic volume. Also, in contrast to a number of reports in older subjects, our findings show only small losses in cardiovascular response, and in left ventricular performance during light through strenuous exercise.Key words: ejection fraction, stroke volume, arteriovenous oxygen difference, [Formula: see text]peak, age.
Insulin resistance of glucose response produced by hepatic denervations
Authors: Xie Hongsheng , Tsybenko Vsevolod A. , Johnson Melanie V. , Lautt W. Wayne
Published: April 2011

This study investigated the glucose response to insulin infused after hepatic denervation. Hepatic denervations were performed on 13 anesthetized cats at different levels: (i) surgical hepatic anterior plexus denervation, (ii) chemical total hepatic denervation by painting phenol on the tissues around the portal vein, bile duct, common hepatic artery, and hepatic ligaments, and (iii) bilateral vagotomy. Sham denervations were performed on 9 animals. Before denervation and after each performance of denervations, insulin (100 mU/kg, iv) was infused. Plasma glucose concentrations were analyzed at 15, 30, 45, and 60 min after insulin infusion. Hepatic anterior plexus denervation produced a significant reduction in insulin effectiveness. Phenol denervation and bilateral vagotomy failed to further significantly alter the level of insulin resistance developed by hepatic anterior plexus denervation. These observations demonstrate that the effect of insulin on glucose regulation is markedly reduced in the absence of hepatic anterior plexus innervation, suggesting that hepatic nerve function is necessary for the normal glucose response to insulin. Furthermore, the hepatic nerves of relevance appear to reach the liver primarily, if not exclusively, by the anterior hepatic plexus.Key words: insulin, glucose, denervation, liver, cat.
Decreases in rat locomotor activity as a result of changes in synaptic transmission to neurons within the mesencephalic locomotor region
Authors: Brudzynski Stefan M. , Wu Michael , Mogenson Gordon J.
Published: April 2011

The mesencephalic locomotor region is defined as a functional region sending signals to the spinal cord generators of rhythmical limb movements for locomotion. It has been shown that the mesencephalic locomotor region plays a critical role in locomotion initiated from the nucleus accumbens or from the subpallidal region. However, there are conflicting data on whether synaptic input from the nucleus accumbens – subpallidal region to the mesencephalic locomotor region mediates locomotion. The purpose of the study was to determine the role of synaptic input to different subregions of the mesencephalic locomotor region in locomotion induced by injecting dopamine into the nucleus accumbens or by injecting picrotoxin into the subpallidal region in freely behaving rats. Synaptic transmission in the mesencephalic locomotor region was eliminated by excitotoxic lesions or was reversibly interrupted by injecting cobalt chloride, which can block synaptic transmission. Excitotoxic lesions or injections of cobalt into subregions of the mesencephalic locomotor region significantly decreased, although did not completely block, locomotion. The most effective sites for cobalt- and lesion-induced reduction in locomotion were consistent with localization of the mesencephalic locomotor region. Effective sites for cobalt and lesions markedly overlapped but were not identical. The results indicate that synaptic transmission within the mesencephalic locomotor region contributes to dopamine- or picrotoxin-induced locomotion.Key words: locomotion, mesencephalic locomotor region, nucleus accumbens, ventral pallidum, dopamine, picrotoxin, excitotoxins, cobalt chloride.
Spinai cord serotonin receptors in cardiovascular regulation and potentiation of the pressor response to intrathecal substance P after serotonin depletion
Authors: Hasséssian Haroutioun , Poulat Philippe , Hamel Edith , Reader Tomás A. , Couture Réjean
Published: April 2011

The aim of this study was to characterize, in conscious rats, the spinal cord 5-hydroxytryptamine (5-HT) receptors involved in mean arterial pressure (MAP) and heart rate (HR) regulation as well as to examine the influence of bulbospinal 5-HT fibers on cardiovascular responses to intrathecal (i.t.) substance P (SP). The i.t. injection of 5-HT or 5-carboxamidotryptamine (5-CT) (5-HT1A, 1B, 1D agonist) reduced MAP and increased HR in a dose-dependent manner. In contrast, the agonists 8-hydroxy-2-(di-n-propylamino)tetraiin (8-OH-DPAT, 5-HT1A agonist) and α-CH3-5-HT (5-HT1C and 5-HT2) only caused a decrease in HR, while the agonist 2-CH3-5-HT (5-HT3) was devoid of cardiovascular effects. The vasodepressor response to 5-CT was antagonized by methiothepin but not affected by mesulergine, ketanserin, propranolol, or yohimbine. However, all five antagonists reduced the HR increase to 5-CT. Ketanserin, propranolol, mesulergine, yohimbine, and methysergide were without effect on resting MAP, while methiothepin reduced MAP. Methiothepin, ketanserin, and methysergide increased resting HR, yet the other antagonists had no effect on this parameter. Rats treated with p-chlorophenylalanine or 5,7-dihydroxytryptamine, but not with 6-hydroxydopamine, exhibited higher resting HR than that of control rats. Although the resting MAP was unaffected, the pressor response to i.t. SP was significantly enhanced by either 5-HT toxin. The results suggest that the receptor mediating the depressor response to 5-HT and 5-CT conforms with the broad pharmacological profile of a 5-HT1-like receptor and is unlikely to be of the 5-HT2 or 5-HT3 subtype. Since the HR response evoked by 5-CT was blocked by antagonists that exhibit affinities for various 5-HT receptor subtypes, it is suggested that a nonspecific blockade or, alternatively, that more than one receptor contributes to this cardiac effect. In addition, the results raise the possibility that a spinal 5-HT input, likely mediated by 5-HT2 receptors, tonically inhibits HR. Hence, an antagonistic interaction between 5-HT and SP is proposed to play a role in the control of arterial blood pressure in the spinal cord.Key words: 5-hydroxytryptamine, 5-HT receptors, substance P, spinal cord, cardiovascular regulation.