bluuebunny/crossref_metadata_2025 huggingface dataset:
Is dieldrin-induced congenital inviability mediated by central nervous system hyperstimulation or by altered carbohydrate metabolism
Authors: Costella John C. , Virgo Bruce B.
Published: April 2011

Carbohydrate metabolism and central nervous sytem (CNS) intoxication were investigated as causes of dieldrin-induced congenital inviability. The 24-h LD50 was calculated using 5-day-old normal mice (CD-1 strain), fasted for 24 h, and gavaged with dieldrin. The LD50, 27 mg/kg, was 5% of the cumulative dose received by the dieldrin-treated, pregnant females. Acutely poisoned pups convulsed and tremored, inviable pups do not. Inviable pups were caesarian delivered on day 18 from dieldrin-treated females (p.o., 2 mg/kg per day, from day 6 to day 18), and aspects of carbohydrate metabolism were measured 0, 19, and 24 h postdelivery. Inviable and control pups weighed the same at all times but the liver weight of inviable pups was reduced by 0, 8, and 21%, at 0, 19, and 24 h, respectively (control: 61, 48, and 41 mg/g body weight). The inviable pups were hypoglycemic at delivery (0.69 vs. 0.95 mg/mL plasma in the controls), at 19 h (0.53 vs. control values of 0.94 mg/mL), and were aglycemic at 24 h (normal pups: 0.32 mg/mL). Liver glycogen, normal in inviable pups at birth (control: 71 mg/g liver), was reduced by 38% at 19 h (control: 19 mg/g) and by 77% at 24 h (control: 4.5 mg/g). Cardiac glycogen was reduced in treated pups only at 24 h (5.5 mg/g vs. control levels of 11.0 mg/g). Muscle glycogen was also reduced only at 24 h (2.2 mg/g vs. control levels of 5.4 mg/g). Prenatal dieldrin did not affect blood lactate, pyruvate, or urea, nor did it alter hepatic lactate dehydrogenase (LDH) or fructose diphosphatase (FDPase) activities. It is concluded that the inviability is not caused by CNS stimulation; it is associated with congenital hypoglycemia, enhanced glycogenolysis, and apparently normal gluconeogenesis.
The effects of hydrogen ion on spinal neurons
Authors: Marshall K. C. , Engberg I.
Published: April 2011

The effects of iontophoretically applied hydrogen ion (H+) on neuronal excitability were studied in the spinal cord of cats. The activity of extracellularly recorded neurons of the dorsal horn was either depressed or enhanced by H+ and in most cases of enhancement there was a preceding phase of depression. During intracellular recordings from motoneurons it was found that H+ application usually caused a hyperpolarization accompanied by an increase in cell input resistance. In a smaller number of cells the hyperpolarization was succeeded by a depolarization that was coupled with a decrease in input resistance. In some neurons it was shown that the depolarizing phase was more prominent and had a shorter latency when larger currents were used to eject H+. The varied reports from earlier studies of excitation or inhibition of neuronal excitability by H+ may be in part explainable by our observations that the effects may depend on the concentrations of H+ used.
Specific effects of α-D,L-aminoadipic acid on synaptic transmission in frog spinal cord
Authors: Padjen Ante L. , Smith Peter A.
Published: April 2011

The sucrose gap technique was employed to investigate both synaptic and amino acid evoked responses from motoneurones or primary afferents of frog spinal cord. α-D,L-Aminoadipic acid (α-D,L-AAD) selectively antagonized responses to acidic amino acids, especially aspartate. The drug was most effective in antagonizing the polysynaptic components of synaptic potentials evoked by dorsal root or lateral column stimulation but had little effect on their monosynaptic components. The ventral root dorsal root potential which is thought to be mediated by a pathway that does not involve acidic amino acids was insensitive to α-D,L-AAD. These data, which were confirmed by intracellular recording from motoneurones, provided further evidence for the role of acidic amino acids in polysynaptic pathways in frog spinal cord.
Effect of ethanol on potassium-stimulated and electrically stimulated acetylcholine release in vitro from rat cortical slices
Authors: Sunahara Geoffrey I. , Kalant Harold
Published: April 2011

The effects of ethanol (EtOH) on potassium and electrically stimulated acetylcholine (ACh) release were compared in rat cerebral cortical slices in vitro. ACh was measured by pyrolysis – gas–liquid chromatography (GLC). Paired samples were incubated with and without 0.11 M EtOH. In the potassium stimulation experiments, cortical slices were serially incubated for three 45-min periods in normal incubation medium followed by two periods in medium containing either 15 or 27 mM K+. In the electrical stimulation experiments, the cortical slices were similarly incubated for three 30-min periods without stimulation followed by two periods of electrical (10 Hz) stimulation. ACh output rose 20% at 15 mM K+ and 160% at 27 mM K+. Ethanol had no effect on spontaneous ACh release and did not influence the ACh response to high K+ stimulation. Electrical stimulation approximately doubled the ACh output but EtOH reduced electrically stimulated ACh release by 50–80%. These findings are compatible with the view that EtOH acts primarily on Na+ influx during the action potential.
The relative distribution of coronary blood flow in rats with moderate and marked left ventricular hypertrophy
Authors: Tomanek Robert J. , Liesveld Jane L. , Laughlin M. Harold , Wangler Roger D. , Wilson Noela C.
Published: April 2011

A reduced capillary density associated with hypertrophy evoked by pressure overload may impose limitations on coronary flow. To determine the effect of moderate and marked left ventricular hypertrophy on regional myocardial blood flow at rest we studied 53 anesthetized, open-chest rats with radioactive 7- to 10-μm microspheres. Spontaneously hypertensive (SHR) and aortic-constricted rats with left ventricular weight to body weight ratios 38 and 92% greater, respectively, than their normotensive controls provided a contrast between two distinct magnitudes of hypertrophy. Blood flow ratios (left ventricular subendocardium to subepicardium and left to right septum) were used as indices of relative distribution of myocardial blood flow.The data show that mean blood flow ratios were similar in hypertrophic and nonhypertrophic hearts despite the limitations of subnormal perfusion pressures inherent in the experimental conditions. Similarly total left ventricular flow per unit mass was not altered by either magnitude of hypertrophy. Thus, it is concluded that circulatory adjustments and cardiac reserve in the hypertrophic myocardium are sufficient to maintain normal distribution of coronary flow under resting conditions, even when cardiac mass increases nearly twofold.
The cardiovascular effect of chloroquine in anaesthetized dogs
Authors: Sofola O. A.
Published: April 2011

Dogs were anaesthetized with sodium pentobarbitone and the effects, on the cardiovascular system, of graded doses of chloroquine were investigated.Intravenous injection of chloroquine from 2 to 4 mg kg−1 produced significant reductions in cardiac contractility, as estimated by measuring the maximum rate of rise of left ventricular pressure, and also in vascular resistance, estimated by measuring the pressure in a femoral artery perfused at constant flow. Heart rate was reduced significantly only when a dose of 4 mg kg−1 was used.The cardiovascular responses observed in the intact animal were also present after cardiac sympathetic block with propranolol and denervation of the limb or after administration of histamine H1 and H2 receptor antagonists. This suggests that the responses were due to the direct action of chloroquine on the heart and blood vessels.
Noradrenaline-induced calorigenesis in warm- and in cold-acclimated rats: relations between concentration of noradrenaline in arterial plasma, blood flow to differently located masses of brown adipose tissue, and calorigenic response
Authors: Foster David O. , Depocas Florent , Frydman M. Lorraine
Published: April 2011

Barbital-sedated, warm-acclimated (WA) or cold-acclimated (CA) rats were infused intravenously with noradrenaline (NA) at doses that elicited graded calorigenic responses. Blood flow (Q) to the various bodies of brown adipose tissue (BAT), the major sites of the NA-induced calorigenesis, was measured with labeled microspheres. The O2 content of arterial blood and of venous blood from interscapular BAT and the concentration of NA in arterial plasma (ANA) were also determined. ANA was linearly related to the dose of NA. Calorigenic response and the Q of total BAT and of separate bodies of BAT were sigmoid functions of ANA. The threshold for calorigenic response or for increased flow to BAT was an ANA of about 2 ng/mL (12 nM), except for some bodies of BAT in CA rats where it was closer to 4 ng/mL. Delivery of O2 to total BAT and calorigenic response were related linearly. The bodies of BAT were heterogeneous in Q per gram and in CA rats the hierarchy in Q per gram changed markedly as ANA and calorigenic response increased. The analysis of these results takes into account that calorigenesis in BAT normally is not mediated by circulating NA, that in NA-infused rats neuronal and extraneuronal uptakes of NA would effect a lower concentration of NA at the adrenoceptors of BAT than in the circulation, and that many factors such as organization and density of adrenergic innervation and the number and efficacy of receptors must have contributed to determining the measured responses of BAT. It is concluded that the differently located bodies of BAT in rats may have significant differences in composition and structure and that they may undergo differential development during cold acclimation.
A comparison of the dipsogenic responses of male and female rats to a variety of stimuli
Authors: Kaufman Susan
Published: April 2011

Female rats subjected to 48 h of water deprivation drank more than similarly deprived males. There was no sexual difference in the dipsogenic responses to intracellular dehydration produced by intravenous hypertonic NaCl but females drank considerably more than males in response to the extracellular stimuli of hyperoncotic polyethylene glycol and angiotensin II. It is concluded that intact adult female rats are dipsogenically more responsive than adult male rats to stimuli acting through the pathways of extracellularly induced thirst but not to those arising from the intracellular fluid compartment.
Effects of barium on gastric microsomal K+-stimulated para-nitrophenyl phosphatase activity
Authors: Ray Tushar K.
Published: April 2011

Ba2+ at low concentrations (1 mM or lower) stimulates the basal and K+-stimulated para-nitrophenyl phosphatase activity associated with the purified microsomal fractions from the oxyntic cells of bullfrog gastric mucosa. However, at higher concentrations Ba2+ acts as a competitive inhibitor of the K+-stimulated phosphatase. Ba2+ alone, in absence of any Mg2+, cannot maintain the enzyme activity; hence Ba2+ can only influence or modulate the Mg2+-dependent phosphatase. The effects are unique for Ba2+ because all other divalent cations such as Ca2+ and Zn2+ act as inhibitors of this enzyme under similar conditions. The data offer a possible biochemical basis for the known pharmacological effects of Ba2+ in gastric acid secretion.
Protein synthesis, amino acid uptake, and pools during isoproterenol-induced hypertrophy of the rat heart and tibialis muscle
Authors: Deshaies Yves , Willemot Joan , Leblanc Jacques
Published: April 2011

Chronic administration of isoproterenol (ISO) produces hypertrophy of the rat heart and tibialis muscle. With doses of 0.1, 0.3, and 0.6 mg/kg, hypertrophy of the heart is significant by the 3rd day of treatment. Maximum cardiac enlargement attained with doses of 0.3 and 0.6 mg/kg occurs after 21 days and averages 40% above control values. ISO increases tibialis muscle weight by 15%. Incorporation of 14C-labeled amino acids into total heart and tibialis muscle protein is stimulated by ISO. Maximum stimulation occurs 2–3 h after the fifth daily injection of ISO. The stimulation of incorporation is greater during the first few days of treatment and decreases gradually thereafter. A single injection of ISO decreases the total amino acid concentration of the serum, heart and tibialis muscle whereas the rate of amino acid uptake by the heart and tibialis muscle is increased by ISO. The production of hypertrophy of the heart and tibialis muscle in diabetic or castrated animals by ISO suggests that insulin and testosterone are not essential in the mechanism of ISO-induced hypertrophy.
Brain norepinephrine, dopamine, and 5-hydroxytryptamine concentration abnormalities and their role in the high seizure susceptibility of epileptic chickens
Authors: Johnson D. D. , Jaju A. T. , Ness L. , Richardson J. S. , Crawford R. D.
Published: April 2011

Norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) concentrations were determined in cerebral hemispheres, optic lobes, the midbrain pons–medulla, and cerebellum of adult homozygous recessive epileptic chickens during interictal periods and compared with concentrations in their nonepileptic heterozygous hatchmates. Cerebral hemispheres from epileptic fowl contained significantly lower concentrations of 5-HT and DA and higher concentrations of NE than nonepileptics. Elevation of 5-HT with phenelzine, tryptophan, or the combination of phenelzine plus tryptophan had no effect on seizure susceptibility or severity. Treatment with L-3,4-dihydroxyphenylalanine, which increased brain DA, also had no effect on the seizure incidence or severity. Administration of phenoxybenzamine, phentolamine, or propranolol to block adrenergic receptors did not reduce seizure susceptibility.
Methylene blue inhibits coronary arterial relaxation and guanylate cyclase activation by nitroglycerin, sodium nitrite, and amyl nitrite
Authors: Gruetter Carl A. , Kadowitz Philip J. , Ignarro Louis J.
Published: April 2011

Relaxation by nitroglycerin, sodium nitrite, and amyl nitrite of bovine coronary arterial smooth muscle was inhibited by the oxidant methylene blue. Methylene blue also inhibited activation of bovine coronary arterial soluble guanylate cyclase by nitroglycerin, which required addition of cysteine. At concentrations less than 10 mM, sodium nitrite required the addition of one of several thiols or ascorbate to activate guanylate cyclase from bovine coronary artery. Guanylate cyclase activation by large amounts (50 μL) of saturated amyl nitrite gas did not require, but was enhanced by, the addition of thiols or ascorbate. However, similar to sodium nitrite, guanylate cyclase activation by smaller amounts (5 μL) of saturated amyl nitrite gas did require the addition of one of various thiols or ascorbate. Methylene blue markedly inhibited guanylate cyclase activation by sodium nitrite in the presence of cysteine or ascorbate and similarly inhibited enzyme activation by amyl nitrite either in the absence or presence of cysteine or ascorbate. These data support the hypothesis that nitrates and nitrites relax vascular smooth muscle by stimulating cyclic GMP formation. The results further suggest that, similar to relaxation and guanylate cyclase activation by nitroso-containing compounds, relaxation and enzyme activation by nitrates and nitrites may involve the formation of nitric oxide or complexes of nitric oxide as active intermediates.
The effects of cofactor and species differences on the in vitro metabolism of propiophenone and phenylacetone
Authors: Coutts R. T. , Prelusky D. R. , Jones G. R.
Published: April 2011

In vitro metabolism of the aromatic ketone propiophenone and its nonaromatic isomer phenylacetone was studied using fortified 12 000 × g supernatants of liver homogenates from rat and rabbit. Reduction to the corresponding alcohols was the major metabolic route observed, although aliphatic C-hydroxylation and alcohol dehydrogenation also occurred. Marked differences were observed in the amounts of carbonyl reduction of the substrates, which was dependant on the species as well as the cofactor employed. Using rat liver preparation, phenylacetone was reduced to 1-phenyl-2-propanol much more efficiently with an NADH-fortified system than when NADPH was used whereas in rabbit, extensive reduction occurred in the presence of either cofactor. Reduction of propiophenone to 1-phenyl-1-propanol by rat liver preparation was slightly greater in the presence of NADH than with NADPH; the converse was observed in rabbit.Aliphatic hydroxylation of propiophenone to 2-hydroxy-1-phenyl-1-propamine was also a significant metabolic pathway in both species, with NADPH being the more efficient cofactor, but C-1 hydroxylation of phenylacetone to 1-hydroxy-1-phenyl-2-propanone occurred only to a minor extent. Small amounts of 1-phenyl-1,2-propanedione, as well as both erythro and threo isomers of 1-phenyl-1,2-propanediol, were also identified as metabolites in both species. Similar metabolic studies were carried out on the alcohols 1-phenyl-1-propanol and 1-phenyl-2-propanol and again the nature and quantities of metabolites isolated showed both species and cofactor dependancies.
Release of noradrenaline from the rat tail artery induced by inhibition of the sodium pump in calcium-free solution
Authors: Palatý Vladimír
Published: April 2011

The release of noradrenaline from the isolated rat tail artery into Ca2+- and K-free, 1 mM ouabain containing solution was measured by means of radioenzymatic method. The rate of noradrenaline release increased gradually reaching a maximum of ca. 2.30 nmol∙g−1∙h−1 after 100 min. The enhancement of noradrenaline release could be inhibited by cocaine and phenoxybenzamine but not by desipramine. The rate of noradrenaline release could be approximately doubled by prior inhibition of monoamine oxidase with pargyline. The release was accompanied by a decline in the proportion of storage vesicles containing an electron-dense core. These observations indicate that, in the absence of external Ca2+, inhibition of the sodium pump causes nonexocytotic release of endogenous noradrenaline.
The effect of starvation on obese mice
Authors: Hahn P. , Skala J. P.
Published: April 2011

Plasma levels of total and acylcarnitine and the activities of carnitine acetyltransferase (CAT) and carnitine, palmitoyltransferase (PCT) in liver and CAT in brown fat were determined in young obese (ob/ob) mice and their littermates during starvation. Plasma levels of acylcarnitine and β-hydroxybutyrate rose equally in both groups. Total carnitine levels, however, decreased in lean and rose in obese animals. Hepatic PCT and phosphoenolpyruvate carboxykinase activities rose more in lean than obese mice and brown fat CAT activity decreased in the obese group. Fatty acid synthetase activity decreased equally in the liver in obese mice and their lean littermates.
Renin substrate in rat mesenteric artery
Authors: Desjardins-Giasson Suzanne , Gutkowska Jolanta , Garcia Raul , Genest Jacques
Published: April 2011

The concentration of renin substrate (RS) was measured in rat mesenteric artery tissue. The concentration of this substrate both in arterial tissue and in plasma was markedly higher in rats 1 day after bilateral nephrectomy than in sham-operated controls, the percentage difference being higher in plasma than in arterial RS. Conversely, the decrease apparently induced 3 days after adrenalectomy (i.e., the difference in RS concentration from sham-operated rats) was greater in arterial tissue than in plasma. This finding may be explained by changes in RS concentrations induced by the sham operation. Sham surgery itself increased plasma RS after 1 day (but not after 3 days) and arterial RS after 3 days (but not after 1 day). There was a positive correlation between arterial and plasma renin substrate concentrations for the overall results but not within individual groups. As renin and angiotensin-converting enzyme activity are also present in arterial tissues, all the necessary components for local generation of angiotensin II have now been shown to be present within the wall of resistance vessels.
A comparison of the effects of flurazepam on γ-aminobutyric acid mediated depression of cerebellar and cerebral cortical neurons
Authors: Jiang Zhi-Gen
Published: April 2011

With standard extracellular recording and microiontophoretic techniques, the effects of flurazepam on γ-aminobutyric acid (GABA) evoked depression of cerebellar and cerebral cortical neurons in rats have been studied. It was found that although flurazepam potentiated the GABA-mediated inhibition of most Purkinje cells (25 of 36), it caused only a weak potentiation of GABA action on some cerebral cortical neurons (14 of 37). The difference between the action of flurazepam in these two structures was statistically significant. The results confirm a previous report that the enhancement of GABA-evoked inhibition by benzodiazepines is more readily elicited on cerebellar cortical neurons than on cerebral cortical neurons.
Classifying sensory patterns and their effects on locomotion and tremor
Authors: Stein R. B. , Gordon T. , Oğuztöreli M. N. , Lee R. G.
Published: April 2011

Methods are described for analyzing the patterns of sensory activity in peripheral nerves during unrestrained behaviour. In locomotion, nerves supplying ankle extensors and flexors typically show two bursts of sensory activity per step cycle. Variations in sensory input may be important in modulating the ongoing oscillation. Altered sensory input may also change the phase of an ongoing oscillation (as in human essential tremor) or may only have a transient reflex effect (as in Parkinsonian tremor). Various types of interactions can be analyzed using a model of the peripheral neuromuscular system and its central connections. In general, the following categories are suggested for sensory actions on neural oscillations: (1) modulation of (a) the amplitude or (b) the frequency; (2) resetting (i.e., a maintained change in the timing of an oscillation without changes in frequency); (3) repatterning an oscillation (a) over several cycles (e.g., gait changes in locomotion) or (b) within a cycle or two (e.g., the stumble corrective reaction); and (4) gating an oscillation on or off.
Comment: A schema for the interactions between motor programs and sensory input
Authors: Tatton W. G. , Bruce I. C.
Published: April 2011

In this overview we utilize and extend a model, originally developed for "command interneuron" control of the generation of motor programs, to discuss the roles sensory inputs play in movement control. To provide a conceptual framework, we present a modular schematic of the motor control and sensory processing apparatus of an hypothetical nervous system. In the schematic, "subroutines" (basic units of motor programs) are seen as "playing out" through switching and sequencing networks to "driver neurons." The "driver neurons" then activate motoneurons to execute the programmed movements. Five modes of interaction between motor programs and sensory input are considered using examples from invertebrate and vertebrate neuronal circuitry. These modes of interaction occur at the following locations: (1) the "program selector," to initiate a motor program; (2) the "motor subroutine directory," advancing the program to the next subroutine; (3) the "driver neurons" and motoneurons, where the "gain" of subroutine instructions can be modulated; (4) the "motor programmer," which monitors programs in progress and provides for program development and updating; and (5) the "driver neurons" themselves, which control sensory processing by "selecting" the appropriate sensory inputs for the program in progress. Mode 5 is illustrated in more detail through a consideration of the modification of stretch receptor input by "extensor" and "flexor" command interneurones in the circuitry controlling postural movements of the crayfish abdomen.
The contribution of sensory inputs to the pattern generation of breathing
Authors: Euler C. von
Published: April 2011

Current concepts of the basic neural control system and its modulation by afferent inputs are reviewed. It is emphasized that, in analogy with locomotion, the central pattern generator (CPG) for automatic metabolic respiration does not depend on any afferent feedback from receptors sensitive to the movements of the "pump," or the streams of pumped air, for its production of a rhythmic motor output provided the CPG receives some "drive" inputs above threshold and adequate bias.The operation of a variety of reflexes and feedback loops is of fundamental importance, however, for adapting the breathing pattern to the varying requirements for gas exchange and to the many behavioural, nonmetabolic demands on the breathing apparatus which are competing with its primary metabolic control functions. The presentation is focussed also on available evidence that the respiratory CPG exerts powerful modulations on the transmission in these reflex pathways controlling the pattern of breathing and adjusting it to the various metabolic and behavioural demands. Mechanisms for "gating," "phasic gain changes," and "phase-dependent reflex reversal" are exemplified.
Comment: Gating effects and constraints on the central pattern generators for rhythmic movements
Authors: Jordan Larry M.
Published: April 2011

Respiration, mastication, and locomotion are compared in terms of the contributions of events occurring at the motoneuron membrane and at premotoneuronal levels for the production of phasic gain changes of afferent effects. Data are presented which suggest that an inhibitory mechanism operating on limb motoneurons can prevent disruption of the locomotor pattern by proprioceptive input and that Ia inhibitory interneurons contribute to this rhythmic inhibition of both flexor and extensor motoneurons. Renshaw cell rhythmic activity during locomotion is described and discussed in terms of its possible role in gating of inputs to motoneurons.
Pharmacological characterization of the vascular permeability enhancing effects of kinins in the rabbit skin
Authors: Marceau F. , Knap M. , Regoli D.
Published: April 2011

We have studied the increase of vascular permeability produced by kinins in rabbit dermis using the measurement of the exudation of a protein-bound dye (Evans blue) following the local injections of peptides.Representatives of four peptide groups having kinin-like pharmacological properties have been tested in this system at doses ranging from 10−12 to 10−9 mol: they are bradykinin (BK), substance P, bombesin, and the C-terminal octapeptide of cholecystokinin. Only BK has appreciable effects at the utilised doses.In order to identify the type of receptor mediating the effect of kinins in this system, the following order of potency of agonist analogues has been measured: [Tyr(Me)8]-BK > kallidin (KD) > BK > des-Arg9-BK. Moreover the B1 receptor antagonist, des-Arg10-[Leu9]-KD, was found to be inactive as inhibitor of the increase of permeability produced by BK. These facts suggest that bradykinin may activate B2 receptors in this system.In order to assess the participation of other endogenous mediators to the effect of BK on vascular permeability, mixed solutions of BK and indomethacin or BK and mepyramine were injected in the rabbit dermis. Indomethacin (0,1 – 1 μg) did not modify the responses to BK while mepyramine (10 μg) significantly reduced the effects of the lowest doses of BK. This finding was taken as an indication of the possible participation of tissue histamine to the increased vascular permeability evoked by BK. It is concluded that the blueing assay of the rabbit dermis is a distinctive system (a) which is specific for BK-related kinins, (b) in which the effects of BK may be mediated by B2 receptors, and (c) in which the action of BK may be partially mediated by histamine but is probably not mediated by arachidonic acid metabolites.
Peptides and the human colon: an in vitro pharmacological study
Authors: Couture R. , Mizrahi J. , Regoli D. , Devroede G.
Published: April 2011

Longitudinal and circular strips of human colon isolated in vitro respond with dose-dependent contractions to angiotensin II, bradykinin, substance P, neurotensin, bombesin, histamine, and carbachol, and are inhibited by the vasoactive intestinal peptide. The octapeptide (26–33) of cholecystokinin contracts only the longitudinal muscle, while 5-hydroxytryptamine (5-HT) contracts the circular and inhibits the longitudinal muscle strip. Opioid peptides, somatostatin, secretin, motilin, glucagon, insulin and the C-terminal tetrapeptide of gastrin are inactive as stimulants or relaxants. The sensitivity of the human colon to des-Arg9-bradykinin, a specific stimulant of B1 receptors for kinins, increases progressively with the incubation time in vitro. The response of the colon to des-Arg9-bradykinin is blocked by [Leu9]-des-Arg10-kallidine (KD), a specific inhibitor of B1 receptors for kinins. The myotropic effect of neurotensin is not antagonised by [D-Trp11]-neurotensin, while that of angiotensin II is blocked by [Leu8]-angiotensin II.Substance P appears to exert its stimulant action through the activation of specific receptors since its effect is not influenced by a variety of inhibitors (atropine, propranolol, methysergide, diphenhydramine, [Leu8]-angiotensin II, [Leu9]-des-Arg10-KD and haloperidol) or by indomethacin and baclofen.The stimulant actions of bradykinin and angiotensin II appear to be due to the activation of specific receptors on the smooth muscle fibers, although indirect actions of these peptides on nervous cells cannot be excluded.Phentolamine and opioid peptides (Met-enkephalin, dynorphin) potentiate the actions of substance P, bradykinin, and angiotensin probably by interfering with the function of the intramural autonomic nervous sytem.
Stimulus–secretion coupling in exocrine pancreas: possible role of calmodulin
Authors: Heisler Seymour , Chauvelot Laurence , Desjardins Diane , Noel Christiane , Lambert Herman , Desy-Audet Louise
Published: April 2011

Many calcium-mediated effects in mammalian cells may be activated by calcium-calmodulin stimulated enzymes. These effects are inhibited by various antidepressant drugs which bind to and inactivate calmodulin. In the current study, calmodulin was identified by affinity chromatography and gel electrophoresis in the cytoplasm of dispersed rat pancreatic acinar cells. Its role in enzyme secretion was assessed by evaluating the effects of various antidepressant drugs on the enzyme secretory process. Chlorpromazine, trifluoperazine, thioridazine, chlorprothixene and amitriptyline inhibited amylase secretion stimulated by carbacol, A-23187, and cholecystokinin-pancreozymin but not that elicitied by dibutyryl cyclic AMP secretin or vasoactive intestinal peptide (VIP). Haloperidol, sulpiride, phenobarbital, and ethanol were without effect on secretagogue-stimulated enzyme release. Only those agents which blocked secretion also inhibited 45Ca release stimulated by carbachol from isotope preloaded cells. The data suggest that calmodulin may have a functional role in pancreatic enzyme secretion.
The vascular sensitizing character of plasma from spontaneously hypertensive rats
Authors: Wright Gary L.
Published: April 2011

Experiments were conducted to examine the effects of plasma from spontaneously hypertensive rats (systolic blood pressure (SBP) = 183 torr; 1 torr = 133.322 Pa) on the contractile properties of aortic strips from normotensive rats. While incubated in plasma from spontaneously hypertensive (SH) rats, the aortic strips of normotensive rats exhibited hyperresponsiveness to norepinephrine (NE) compared with those incubated in plasma obtained from Wistar–Kyoto (SBP = 128 torr) or Sprague–Dawley (SBP = 110 torr) rats. The washout of plasma and perfusion of the aortic strips with Krebs bicarbonate solution abolished the effect of SH plasma on the reactivity to NE but not potassium, suggesting a residual hypersensitivity. The comparison of these findings with results obtained for contractions of aortic strips in Krebs bicarbonate solution containing high and low levels of calcium indicated the effect of SH plasma on vascular tissue sensitivity was not directly related to an alteration in plasma levels of calcium.
Effect of digitonin on rat myometrium subcellular membrane fractions
Authors: Grover A. K. , Kwan C. Y. , Crankshaw J. , Daniel E. E.
Published: April 2011

Isopycnic centrifugation experiments using sucrose density gradients showed that in digitonin-treated microsomes the distribution of the plasma membrane (PM) marker 5′-nucleotidase was shifted to higher densities. The treatment also caused similar but less pronounced changes in the distribution of protein, the putative endoplasmic reticulum (ER) marker NADPH-dependent cytochrome c reductase, and the inner mitochondrial marker cytochrome c oxidase. Similar experiments using more purified membrane fractions showed that the digitonin treatment led to a comparable increase in the densities of the fractions N1 and N2 previously described as subfractions of plasma membrane and to considerably less increase in the density of the fraction N3B which is enriched in the endoplasmic reticulum and the inner mitochondrial markers. Digitonin inhibited the ATP-dependent Ca uptake by the N1 fraction in a concentration-dependent manner (I50 = 0.3 mg/mL). Digitonin (0.5 mg/mL) inhibited the ATP-dependent azide-insensitive Ca uptake by all the fractions. The results support the hypothesis that (a) N1 and N2 are subfractions of plasma membrane, and (b) ATP-dependent azide-insensitive Ca uptake in rat myometrium is a property of plasma membranes.
Lethal factor in the male mouse submandibular gland
Authors: Hatakeyama Keiko , Hiramatsu Masahiko , Minami Naomi
Published: April 2011

The presence of a toxic component (lethal factor) has been reported in the male mouse submandibular gland (SMG). This study was designed to clarify whether the toxic component was secreted into saliva or not and to investigate some characteristics of the component. Not only SMG extract but also phenylephrine-induced saliva from male mice was highly toxic to guinea pigs, rats, hamsters, and mice. The toxic activity of the saliva was found in all strains of male mice examined. In female mice, the toxic activity was extremely low. One of the toxic components in the saliva was purified by isoelectric focusing and DEAE Sephadex A-50 chromatography and identified with a kallikrein-like enzyme. The activity of the enzyme markedly increased in saliva secreted to α-adrenergic agents but not to β-adrenergic or cholinergic agents. These results indicate that the lethal factor in the male mouse SMG is an exocrine protein with kallikrein activity and its secretion into saliva is controlled through α-adrenergic receptors.
Effect of phenobarbital on sleep and nighttime plasma growth hormone and Cortisol levels
Authors: Prinz Patricia N. , Vitiello Michael V. , Roehrs Timothy A. , Linnoila Markku , Weitzman Elliott D.
Published: April 2011

The acute and chronic effects of phenobarbital and phenobarbital withdrawal on sleep patterns and on plasma growth hormone (GH) and Cortisol fluctuations occurring during sleep were studied. Before bed, five healthy men, aged 21 to 25, were given a placebo on three baseline nights, phenobarbital (100 mg p.o.) for nine nights, and a placebo on a final withdrawal night. Beginning on the third of three consecutive nights in the laboratory, all-night polygraphic sleep recordings and blood samples (obtained every 20 min through indwelling venous cannulae) were collected for the placebo, acute phenobarbital, chronic phenobarbital, and phenobarbital withdrawal conditions.Blood phenobarbital levels ranged between 5 to 9 μg/100 mL across all hours of the chronic drug night. At this low sedative dose, latency to sleep onset and stage 4 sleep were significantly reduced in the chronic drug condition, but REM sleep was not significantly reduced. No significant sleep change was observed on the withdrawal night. Both peak GH level and total integrated GH across the night were unaffected by the acute, chronic, and withdrawal conditions. The pattern of GH release appeared to be altered on the phenobarbital and phenobarbital withdrawal nights as compared with placebo. Nighttime plasma cortisol levels were not significantly altered by any experimental condition.
Multiple binding sites for [3H]clonidine and [3H]WB-4101 in rat brain
Authors: Weinreich Pnina , Chiu Andrew , Warsh Jerry , Seeman Philip
Published: April 2011

Binding of the α-adrenergic agonist [3H]clonidine and the α-adrenergic antagonist [3H]WB-4101 exhibited multiple binding site characteristics in both rat frontal cortex and cerebellum. Kinetic analysis of the dissociation of both radioligands in rat frontal cortex suggests two high affinity sites for each ligand. Competition of various noradrenergic agonists and antagonists for [3H]WB-4101 binding yielded shallow competition curves, with Hill coefficients ranging from 0.45 to 0.7. This further suggests multiplicity in [3H]WB-4101 binding. In the rat cerebellum, competition of various noradrenergic drugs for [3H]clonidine binding yielded biphasic competition curves. Furthermore Scatchard analysis of [3H]clonidine binding in rat cerebellum showed two high affinity sites with KD = 0.5 nM and 1.9 nM, respectively. Competition of various noradrenergic drugs for [3H]WB-4101 binding in the rat cerebellum yielded biphasic competition curves. Lesioning of the dorsal bundle with 6-hydroxydopamine did not significantly affect the binding of either [3H]clonidine or [3H]WB-4101. These findings for both [3H]clonidine and [3H]WB-4101 binding in rat frontal cortex and cerebellum can be explained by the existence of postsynaptic binding sites for both 3H ligands.
The reversal of hemorrhagic hypotension by naloxone in conscious rabbits
Authors: Schadt James C. , York Donald H.
Published: April 2011

The effects of naloxone on blood pressure and heart rate were studied in consious, chronically prepared rabbits. In addition, the effects of barbiturate anesthesia on the response to naloxone were investigated. Initial surgery to implant arterial and venous catheters was performed under halothane anesthesia. Experiments were begun 10 days to 2 weeks later. The rabbits were divided into two groups: a normotensive group and a group made hypotensive by hemorrhage. In the normotensive rabbits, naloxone (2 mg/kg i.v.) did not alter mean arterial blood pressure [Formula: see text], pulse pressure, (PP), or heart rate (HR). However, a 5 mg/kg dose increased [Formula: see text] and PP, and decreased HR. In the hypotensive group, naloxone in a dose of 2, 3, or 5 mg/kg i.v. significantly increased [Formula: see text] and PP while decreasing HR in a dose-related manner. A dose of 0.2 mg/kg did not significantly alter any of the measured parameters. Pentobarbital anesthesia significantly reduced the effects of the 3 mg/kg naloxone dose in the hypotensive group. These actions of naloxone may be mediated through antagonism of endogenous opiates.
Triazene metabolism. I. The effect of substituents in the aryl group on the kinetics of enzyme-catalysed N-demethylation of 1-aryl-3,3-dimethyltriazenes
Authors: Godin James R. P. , Vaughan Keith , Renton Kenneth W.
Published: April 2011

A series of antitumor dimethylaryltriazenes (ArN=N∙NMe2) have been studied with respect to enzyme catalysed N-demethylation by liver microsomes and the Km values determined by Lineweaver–Burk treatement. The substituent in the aryl group of the triazene does not significantly effect the magnitude of Km, which is of the same order of magnitude as the Km for aminopyrine. On the other hand, dimethyltriazenes appear to have lower Km values for demethylation than the structurally similar dimethylnitrosamines. Monomethyltriazenes, the proposed active metabolites of the dimethyltriazenes, do not undergo appreciable demethylation in the presence of microsomes and it appears that the dimethyltriazenes only demethylate once during metabolism. Spontaneous formaldehyde release from the hydroxymethyltriazene in the presence of the Nash reagent prevented an analogous study of the metabolism of these compounds.
Altered concentration of catecholamines in the hypothalamus of the rat after renal denervation
Authors: Calaresu Franco R. , Ciriello John
Published: April 2011

Concentrations of noradrenaline, adrenaline, and dopamine were measured using a sensitive radioenzymatic assay in hypothalamic nuclei of rats 4 days after bilateral renal denervation. After renal denervation, catecholamine levels in several hypothalamic nuclei were found to be different from those of sham-operated animals. Noradrenaline was found to be increased in the supraoptic nucleus, adrenaline was increased in the paraventricular nucleus and lateral hypothalamic area, and dopamine was decreased in the supraoptic nucleus, medial preoptic nucleus and lateral hypothalamic area. These data suggest that afferent renal fibers influence the metabolism of hypothalamic catecholamines and that neural information originating in the kidney and transmitted to the hypothalamus is probably involved in physiological responses related to cardiovascular adjustments and body fluid balance.
Cardiac atrial factor—an endogenous diuretic?
Authors: Sonnenberg H. , Chong C. K. , Veress A. T.
Published: April 2011

An extract of rat heart atria causes a saluresis in bioassay rats. When organic acid secretion in the proximal tubule was blocked by probenecid, the saluretic response to the extract was significantly reduced. Similarly, the natriuretic response to acute hypervolemia was reduced by probenecid administration. The data indicate that the atrial natriuretic factor, like the "loop" diuretic drugs, requires proximal tubular secretion for maximal renal activity. Furthermore, the factor may play a role in the renal response to acute blood volume expansion.
The Upjohn Award Lecture 1981/La Conférence Upjohn 1981: The metabolism of xenobiotics in different populations
Authors: Kalow W.
Published: April 2011

This paper provides a broad review of the topic, but particularly emphasizes the definition of genetic factors that may cause interethnic differences in the capacity to metabolize drugs and toxic chemicals and recent case studies of dehydrogenases and mixed function oxidases.
Functional capillary density in normal and transplanted rat hearts
Authors: Korecky B. , Hai C. M. , Rakusan K.
Published: April 2011

The subepicardial capillaries were visualised under normoxemia and hypoxemia by cinemicrophotography of the beating heart in open-chest rats. The functional intercapillary distances (ICD) were directly measured from focused frames. Under normoxemia, the average ICD was 19.2 μm and under hypoxemia, 17.9 μm (p < 0.01). This decrease of 1.3 μm under hypoxemia corresponds to an average recruitment of an additional 416 capillaries/mm2 (from 2762 to 3178).During postnatal development, both the normoxemic and hypoxemic ICD's increased with left ventricular weight. The regression analysis of this relationship indicates that the hypoxemic ICD's remain significantly shorter within the observed range.In heterotopicall y isotransplanted, empty, beating rat hearts, there was no difference in functional ICD between normoxemia and hypoxemia either in 1-day-old (18.5 versus 18.6 μm) or in 7-day-old (17.1 versus 17.1 μm) transplants.Unlike the hearts in situ which could be observed only through a long working distance, low power objective (11×), the heterotopic transplants could also be observed through a higher power (22×) lens with an optical penetration of less than 5 μm. On the same hearts almost identical ICD's were obtained by both lenses during normoxemia and hypoxemia. Therefore, recruitment of capillaries observed on the normal hearts could not be due to different optical characteristics of the hypoxemic myocardium.
Effect of sodium- or chloride-deficient medium on fast axonal transport in frog spinal nerves
Authors: Lavoie P.-A.
Published: April 2011

Fast axonal transport of radiolabeled proteins was studied in vitro in desheathed spinal nerves from frog. The replacement of the NaCl of the medium by LiCl reduced by 58% the amount of radiolabeled proteins which accumulated at a ligature, but its replacement by choline chloride did not inhibit transport. The replacement of NaCl by sodium isethionate led to a 32% reduction in the quantity of protein-bound radioactivity at the ligature. The results suggest that Cl ions are essential to maintain fast axonal transport, and that Na+ may also be important.
The effects of metabolic inhibitors on the contraction of creatine-depleted muscle
Authors: Mainwood G. W. , Alward M. , Eiselt B.
Published: April 2011

Rats were fed on a diet containing 1% β-guanidinopropionate (Gp) to deplete their muscles of creatine. The apparent energy reserves (creatine phosphate (CrP) + ATP) of rested state diaphragm muscle strips were found to be 79% depleted by this treatment. To determine if the effective energy reserves for contraction were depleted to a similar extent, the response to direct electrical stimulation (0.2-s tetani) was measured in the presence of inhibitors of respiration (NaCN) and glycolysis (iodoacetate). Only 4 ± 1 contractions could be elicited from strips from Gp-fed animals. Normal strips gave 15 ± 2 contractions under the same conditions. For both sets of diaphragms the energetic cost of contraction in terms of ~P was approximately 1 μmol/g wet weight. The mean level of Pi generated following stimulation to exhaustion was 10.1 μmol/g more in normal than in depleted strips. It is concluded that no significant additional energy stores such as phosphorylated Gp are readily available for contraction in muscles depleted of creatine by Gp treatment.
Urea handling by the distal tubule and collecting duct of the rat during urea–saline, isotonic saline, or urea diuresis
Authors: Sonnenberg H. , Wilson D. R.
Published: April 2011

The aims of the present study were to examine the effects of urea and isotonic saline loads separately and together on urea handling in the medullary collecting duct and surface distal tubules of the rat kidney. Microcatheterization of the medullary collecting duct during isotonic saline diuresis (saline at 5% of body weight per hour, plasma urea 4.3 mM/L), showed an increase in the remaining fraction of filtered urea from 56.2% at the beginning (corticomedullary junction) to 68.5% at the end (papillary tip) of the medullary collecting duct (n = 17 paired samples in six rats, p < 0.05). There was no change in the fraction of filtered urea along the medullary collecting duct during urea diuresis (plasma urea 87 mM/L, n = 15 paired samples in six rats) or during urea–saline diuresis (plasma urea 103 mM/L, n = 32 paired samples in nine rats). Micropuncture of surface distal tubules in the same animals showed an increase in the fraction of filtered urea between end-distal samples and the beginning of the medullary collecting duct from 28.9 to 56.2% during isotonic saline diuresis (p < 0.001), and from 53.6 to 75.3% during urea–saline diuresis (p < 0.01), but no change during urea diuresis (63.6 to 60.0%, p = NS). Our conclusions are as follows. (1) Urea entry into the medullary collecting duct during steady-state diuresis occurs at low intratubular urea concentrations (isotonic saline diuresis) but not at high concentrations (urea–saline diuresis and urea diuresis). (2) Urea entry between the surface distal tubule and the beginning of the medullary collecting duct occurs during saline diuresis (isotonic saline diuresis and urea–saline diuresis) but not urea diuresis. The latter finding suggests that isotonic saline loads affect urea transport differently in juxtamedullary nephrons compared to superficial nephrons.