bluuebunny/crossref_metadata_2025 huggingface dataset:
Differing estrogenic activities for the enantiomers of o,p′-DDT in immature female rats
Authors: McBlain W. A. , Lewin V. , Wolfe F. H.
Published: April 2011

Female rats (20–21 days) were given single intraperitoneal injections of (±)-o,p′-DDT, (−)-o,p′-DDT, or (+)-o,p′-DDT. At 18 h their uteri were excised and the estrogen-sensitive parameters, uterine wet weight, and uterine glycogen content were measured. For o,p′-DDT, the levo enantiomer is the more active estrogen in immature female rats. Optical resolutions of other racemic environmental xenobiotics may be important in the evaluation of their biological effects.
Further identification of PGE1 metabolites formed in the cat lung
Authors: Cozzini B. O. , Dawson C. A.
Published: April 2011

Tritium-labeled compounds appearing in the venous effluent of isolated blood perfused cat lungs after infusion of [3H]prostaglandin E1 (PGE1) appear to be unchanged [3H]PGE1 and 13,14-dihydro-15-keto-PGE1. No 15-keto-PGE1 could be detected in the venous effluent.
Effects of acetylcholine on potassium-induced changes of water and sodium uptakes in cerebral cortex slices from the rat
Authors: Benjamin A. M. , Quastel J. H.
Published: April 2011

The increases in uptakes of water and of sodium ions that occur in rat brain cortex slices when they are incubated in a physiological saline – glucose medium in presence of a high concentration of potassium ions (105 μequiv./ml) are abolished by acetylcholine in presence of eserine but not by choline. Acetylcholine is effective at 20 μM but its optimal effect occurs at about 0.7 mM. Its action is suppressed by atropine and not by d-tubocurarine. The potassium-induced change of permeability of brain cell membranes to sodium ions occurs at a site different from the tetrodotoxin-sensitive channel of sodium entry, because the suppressive effects of acetylcholine and tetrodotoxin are apparently independent of each other. The acetylcholine effect does not occur in the absence of calcium ions from the incubation medium. It is suggested that the increase of cell calcium ions, brought about by high concentrations of potassium ions in the incubation medium, induces an increase of glial permeability to sodium ions, with a resultant change in the sodium gradient, and that this increase is suppressed by acetylcholine.
Production of slow α2-globulin in the pregnant rat
Authors: Kirkcaldy Margaret , Beaton George H.
Published: April 2011

Slow α2-globulin (Sα2G), a high molecular weight glycoprotein, appears as a component of rat serum in a wide variety of both physiologic and pathologic conditions, including pregnancy; it is also present in the neonate. In the present study, the protein was detectable in serum after 6 to 10 days, and was present at moderate levels on day 13, and thereafter through the rest of pregnancy. From immunofluorescent localization and 14C-labelled amino acid incorporation studies, sα2G was found to be localized in uterine and placental tissues and to be synthesized by these tissues as early as day 6 of gestation. Production continued throughout pregnancy. Synthesis in the liver of the pregnant rat began at day 17 of gestation, which is in contrast with the observation in pathologic conditions that liver synthesis is an initial source of the serum protein; substantial fetal liver synthesis was occurring at day 21 of gestation, and the amount in fetal serum was four times greater than that in maternal serum at that time. It is likely that the fetal liver produces sα2G as soon as it begins to function.
Plasma and tissue levels of dietary radiotocopherols in the harp seal, Phoca groenlandica
Authors: Engelhardt F. R.
Published: April 2011

Plasma and tissue levels of dietary radiotracer-labelled tocopherols were examined in the harp seal, Phoca groenlandica. The d-α form showed much higher plasma maxima and retention than d,l-γ-tocopherol. Concentration peaks occurred somewhat later but were greater when the vitamin was fed with Tween 80 than with herring and corn oil respectively. Greater plasma levels occurred with the use of herring oil as compared with corn oil. Seals previously maintained on a vitamin E deficient diet showed greater plasma maxima than seals not so deprived. Plasma and tissues generally showed maximum levels within 24 h postingestion. Tissue levels of labelled dietary α-tocopherol were examined by biopsy and postmortem studies in selected tissues of vitamin E deprived seals.
GABA and glycine actions on spinal motoneurons
Authors: Krnjević K. , Puil E. , Werman R.
Published: April 2011

Applied microiontophoretically in the spinal cord of cats, glycine is consistently more powerful than γ-aminobutyric acid (GABA) in raising the membrane conductance of lumbosacral motoneurons (mean ratio of equipotent iontophoretic currents tested on same cells is 5.6:1). This is the reverse of the situation in cerebral cortex. The effect of glycine is well maintained during applications lasting about 1 min, but that of GABA, after an early peak, drops to a much lower plateau (mean plateau-over-peak ratio is 0.23). The reversal potentials for the action of GABA and glycine are initially similar but they behave differently during a prolonged application; that for glycine usually remains constant or becomes more negative whereas that for GABA tends to shift in the positive direction. Various explanations of these phenomena are considered. It is suggested that a single process, electrogenic uptake of GABA, may account for both desensitization (by removing GABA from its site of action) and the positive shift in GABA reversal potential (because uptake is probably associated with an influx of Na+).
Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat
Authors: Hughson Richard L. , Sutton John R. , Fitzgerald J. Desmond , Jones Norman L.
Published: April 2011

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose–response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.
Epileptiform seizures in domestic fowl. VI. Plasma phenobarbital concentrations and anticonvulsant activity
Authors: Johnson D. D. , Davis H. L. , Bailey D. G. , Crawford R. D.
Published: April 2011

The relationship between plasma phenobarbital concentrations and anticonvulsant activity was determined against seizures induced in epileptic chickens by intermittent photic stimulation (IPS). Intraperitoneally administered phenobarbital produced a plasma-concentration-dependent reduction in both the incidence and severity of seizures. Complete protection against IPS-induced seizures was observed for a period of 6 h after acute phenobarbital administration during which the mean plasma phenobarbital concentrations were between 16.2 ± 0.91 and 13.6 ± 1.0 μg/ml. Plasma phenobarbital concentrations below 3.6 ± 0.06 μg/ml had no measurable effect.
A pharmacological study of SRS-A on the bovine cutaneous vasculature
Authors: Burka J. F. , Eyre P.
Published: April 2011

Bovine slow-reacting substance of anaphylaxis (SRS-A) is capable of producing dose-dependent vascular permeability changes in the skin of calves. The wheals are well-defined indurations, similar to wheals induced by histamine but different from those induced by prostaglandin (PG) E2. Three proposed SRS-A receptor blockers (i.e., FPL 55712, PR-D-92-EA, and sodium meclofenamate) were studied with respect to their antagonism of wheals induced by SRS-A, histamine, and PGE2. PR-D-92-EA and FPL 55712 antagonized SRS-A, and also histamine and PGE2 at high concentrations. Meclofenamate was ineffective against SRS-A but antagonized histamine and PGE2 at higher concentrations. The significance of these results, especially with respect to passive cutaneous anaphylaxis, is discussed.
Muscarinic feedback inhibition of acetylcholine release from the myenteric plexus in the guinea pig ileum and its status after chronic exposure to morphine
Authors: Sawynok Jana , Jhamandas Khem
Published: April 2011

Atropine (10−8–10−6 M) produced a dose-related increase in the release of ACh from the electrically stimulated longitudinal muscle – myenteric plexus preparation. This increase in release was frequency dependent, being greater at low frequencies of stimulation where the pulse release of ACh was greater than at high frequencies. The muscarinic agonist oxotremorine (up to 100 μM) did not inhibit ACh release although 100 μM oxotremorine did antagonize the ability of atropine to increase release. The effect of chronic exposure to morphine, both in vivo and in vitro, on the reactivity of muscarinic receptors mediating this increase was examined. Neither the control rate of ACh release nor the dose–response curve for atropine were altered by (a) an 8-day morphine injection schedule, and (b) exposure of the tissue to morphine in the bath for 90 min. The results of this study support the existence of a muscarinic feedback mechanism which controls ACh release from the myenteric plexus. Chronic exposure to morphine does not produce specific changes in the muscarinic receptor mediating this inhibition.
Depression of glutamate-mediated synaptic transmission by benzyl alcohol
Authors: Colton Carol A. , Colton Joel S.
Published: April 2011

The data obtained from this study suggest that the nonionizable anesthetic benzyl alcohol has two prominent actions on GABA- and glutamate-mediated synaptic transmission at the lobster neuromuscular junction. They are as follows: (1) depression of the excitatory end-plate potential and the postsynaptic membrane response to applied glutamate, and (2) a hyperpolarization of the postsynaptic resting membrane potential associated with a decrease in effective membrane resistance. No change in amplitude of the inhibitory end-plate potential or inhibitory reversal potential was seen. Excitatory miniature end-plate potential frequency was also unaffected. The depression of excitatory synaptic transmission appears to be due to a decreased responsiveness of the postsynaptic receptor–ionophore complex.
Cannabinoid effects on adenylate cyclase and phosphodiesterase activities of mouse brain
Authors: Dolby Thomas W. , Kleinsmith Lewis J.
Published: April 2011

The experiments presented in this paper examine the mechanisms underlying the ability of cannabinoids to alter the in vivo levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in mouse brain. It was found that changes in cyclic AMP levels are a composite result of direct actions of cannabinoids on adenylate cyclase (EC 4.6.1.1) activity and indirect actions involving the potentiation or inhibition of biogenic amine induced activity of adenylate cyclase. Furthermore, the long-term intraperitoneal administration of 1-(−)-Δ-tetrahydrocannabinol to mice produced a form of phosphodiesterase (EC 3.1.4.17) in the brain whose activity is not stimulated by Ca2+, although its basal specific activity is similar to that of control animals. In vitro, the presence of the cannabinoids caused no significant changes in activity of brain PDE at the concentrations tested. Some correlations are presented which imply that many of the observed behavioral and physiological actions of the cannabinoids in mammalian organisms may be mediated via cyclic AMP mechanisms.
Actions of microiontophoretically applied ibotenate on cat spinal interneurones
Authors: MacDonald J. F. , Nistri A.
Published: April 2011

Microiontophoretic applications of ibotenate, an amino acid analogue of glutamate, evoked biphasic responses from single dorsal horn interneurones of the cat spinal cord, i.e., an initial increase in the firing rate followed by a sustained depression of spontaneous firing. A reduced cell sensitivity to excitatory amino acids or peripheral field stimulation was also found during the ibotenate-induced depression. These effects were not produced by glutamate, quisqualate, or kainate, although occasional transient reductions of spontaneous cell firing were observed after application of glutamate. It is suggested that ibotenate might act on inhibitory as well as excitatory receptors of cat spinal interneurones.
Antagonism of conditioned salivation in conscious dogs by antihypertensive drugs
Authors: Sweet Charles S. , Gaul S. Lee
Published: April 2011

Methyldopate (methyldopa (ethyl ester)), carbidopa, clonidine, and ST-91 were evaluated for their effects on conditioned salivation in unanesthetized dogs. Clonidine produced dose-dependent inhibition of salivation 20 min after an intravenous injection. At equivalent and larger doses, ST-91, a clonidine analog which does not penetrate the blood–brain barrier, was ineffective in inhibiting conditioned salivation, suggesting that central rather than peripheral mechanisms are involved in clonidine-induced inhibition of salivation. Methyldopate also produced a dose-dependent inhibition of salivation in dogs. The mechanism involved in methyldopa-induced inhibition of salivation may involve both central and peripheral mechanisms because carbidopa, an inhibitor (like methyldopa) of peripheral aromatic decarboxylase (EC 4.1.1.28), significantly inhibited salivation.
Quantitative study of α-adrenergic receptors in circular and longitudinal muscle of isthmus of rabbit fallopian tube and in rabbit aorta
Authors: Rajkumar K. , Sharma P. L.
Published: April 2011

The affinity of phenylephrine (pD2 value) and KB value for phentolamine for the α-adrenergic receptors of circular and longitudinal muscle of isthmus of rabbit fallopian tube and rabbit aorta have been estimated. The affinity of both phenylephrine and phentolamine was significantly more for the α adrenoceptors of the longitudinal muscle of isthmus of rabbit fallopian tube and rabbit aorta than circular muscle of isthmus of fallopian tube.The results of this investigation suggest that α adrenoceptors of circular muscle of isthmus are atypical. If this holds good for the human fallopian tube, the development of selective α-adrenergic-receptor agonists and antagonists may be of potential practical application for the control of fertility.
Species and strain differences in the lethal factor of the mouse submandibular gland
Authors: Huang J. C.-C. , Hoshino K. , Kim Y. T. , Chebib F. S.
Published: April 2011

The differences in susceptibility of animals to the lethal factor extracted from the mouse submandibular gland and magnitude of its lethality were compared among various species, strains, ages, and sex of mice. Comparisons of LD30 values computed by an IBM 360/System computer using a programmed probit analysis yielded the following significant results. The lethal factor of adult male mice was lethal to all species and strains of animals tested. Strain differences were observed in five inbred strains of mice, and varying degrees of resistance against the lethal factor were demonstrated. The lethality was strongest in the submandibular gland of our subline BALB/c mice, and the highest susceptibility to the lethal factor was demonstrated by female C57BL mice. This factor was found to be lethal not only to mice but also to other species of animals, Mongolian gerbils being most susceptible and New Zealand rabbits next.
Heparin and sulfated mucopolysaccharides—a micro system for quantitative differentiation and determination
Authors: Jaques Louis B. , Sue Tak K. , McDuffie Norman M. , Wice Sandra M.
Published: April 2011

Heparin (Hep), hyaluronic acid, chondroitins (sulfate) A, B, and C, and heparitins (sulfate) A, B, C, and D were subjected to microelectrophoresis in barbital–agarose gel, fixed with cetylpyridinium chloride and stained with toluidine blue. The optical densities of the resulting bands were compared with optical densities obtained upon reaction with azure A in aqueous solution and with the carbazole reagent. A linear relation was obtained between optical density and concentration of purified sulfated mucopolysaccharide (SMP). Less than 1 μg of Hep and 2 μg of other SMPs are required for measurement by electrophoresis, while about 30 μg of each is required with the carbazole reagent. The optical density of a mixture of SMPs was equal to the sum of the densities for the individual SMPs upon microelectrophoresis. It was demonstrated that the individual SMPs in mixtures were distinguished by reaction with specific enzymes and by changes in migration in agarose with barbital, phthalate, ethylenediamine, or propane-diamine buffers, permitting ready demonstration and quantitation of various SMP species. Examples are shown of the application of the procedure to measure the total SMPs and individual SMPs in tissue extracts. The method is sensitive, reproducible, flexible, and measures quantities [Formula: see text] of those measured colorimetrically, yet is relatively unaffected by protein, carbohydrate, or inorganic electrolytes.
The effect of ouabain on the guinea pig ileum longitudinal smooth muscle: 2. Intracellular levels of Ca, Na, K, and Mg during the ouabain response and the dependence of the response on extracellular Ca
Authors: James M. R. , Roufogalis B. D.
Published: April 2011

Isotonic Tris–HCl containing 10 mM LaCl3 at 4 °C effectively removed extracellular ions in 30 min while preventing loss of intracellular ions. Intracellular Ca and Na increased during the contraction in the presence of 10 mM ouabain and then decreased during relaxation. Intracellular Na increased again during the latter part of the relaxation phase when K loss became apparent. Mg levels remained essentially constant. Ouabain responses were rapidly lost in Ca-free medium indicating that they were dependent on extracellular Ca. A 5.5-fold increase in the normal levels of extracellular K did not reduce the contraction to a submaximal dose of ouabain. A full phasic response to high K (60 mM) was observed after a 10-min exposure of the tissue to ouabain, at which time the ouabain response had returned to basal tension. The contraction to ouabain appears to be dissociated from inhibition of the Na,K-ATPase at the K site. The changes in intracellular ions indicated that ouabain contracted the muscle by increasing the plasma membrane permeability to Ca and Na and later decreased the K and Na concentration gradients, probably by inhibition of the Na,K-ATPase.
The interventricular septum: an isolated perfused model for assessing myocardial function
Authors: Bayliss C. E. , Crawford F. B. , Nsafoah B.
Published: April 2011

Classical models for assessing myocardial function suffer from either a potentially anoxic central core or an unsophisticated perfusion system. We have improved Langer's perfused interventricular septum model by adapting it for parabiotic resuscitation, thus achieving rapid stability and significantly less edema. The new model, which consists of a triangular piece of rabbit interventricular septum, perfused through its septal artery, first undergoes a stabilization period of 30 min during parabiotic perfusion from another rabbit. An arteriovenous shunt is then opened and the preparation remains stable for 2 h of perfusion in which fresh blood is recirculated nonparabiotically. It is proposed that during this period, experimental interventions could be undertaken using each septum as its own control. The behaviour of 66 preparations was consistent with classical concepts of myocardial function.Simple measurements were identified for beat-to-beat functional assessment. Contractility was measured by maximum active tension and maximum differential of tension. Relaxation was measured by maximum negative differential of tension and, in the presence of ischemic contracture, changes in resting tension. Compliance was measured by septal length at a specified resting tension. Perfusability was measured by the relationship between pressure and flow.
Some biophysical and biochemical properties of poly (phthaloyl L-lysine) microcapsules containing hemolysate
Authors: Arakawa Masayuki , Kondo Tamotsu
Published: April 2011

Measurements of oxygen equilibrium, zeta-potential, resistance to flow, carbonic anhydrase activity, and catalase activity were made on sheep erythrocyte hemolysate-loaded poly (phthaloyl L-lysine) microcapsules (artificial red blood cells) prepared by an interfacial polycondensation technique. The measurements revealed that oxygen dissociation equilibrium, zeta-potential, and carbonic anhydrase activity of the microcapsules are almost the same as those of sheep erythrocytes, while the microcapsules have a higher resistance to flow and a lower catalase activity than the erythrocytes. Possible ways of improving the properties of the microcapsules were suggested.
The nature of adrenoceptors in the guinea pig cerebral cortex: a microiontophoretic study
Authors: Stone T. W. , Taylor D. A.
Published: April 2011

1. Noradrenaline, isoprenaline, and phenylephrine have been applied my microiontophoresis to neurones in the guinea pig cerebral cortex. All three compounds produced depression of neuronal firing, and all could be antagonized to some extent by phentolamine or propranolol.2. The responses to isoprenaline were substantially reduced in size after a few applications. Noradrenaline and phenylephrine responses were partially reduced at the time of isoprenaline insensitivity, and the responses could now be blocked completely by phentolamine.3. The results suggest that two kinds of receptors are present in the guinea pig cerebral cortex, with properties similar to α and β receptors in the periphery. A single receptor with intermediate properties would not readily explain the present results.4. The results are not consistent with the proposal that α receptors mediate neuronal excitation, and β receptors inhibition in the cerebral cortex.5. It is also suggested that the failure of some previous studies on guinea pig cortex in vitro to demonstrate the presence of β receptors may be due to the particularly rapid desensitization of these receptors.
Noradrenaline-induced calorigenesis in warm- and in cold-acclimated rats: The interrelation of dose of noradrenaline, its concentration in arterial plasma, and calorigenic response
Authors: Depocas Florent , Behrens W. A. , Foster D. O.
Published: April 2011

Barbital-sedated, warm-acclimated (WA) or cold-acclimated (CA) rats were infused intravenously with noradenaline (NA) at doses of 0, 2.5, 5.0, and 10 ng min−1 g−0.74 body weight during a period of 30 min. Concentration of NA in arterial plasma, O2 consumption. and rectal temperature were measured before, during, and after NA infusion. Upon infusion of NA, plasma NA increased rapidly to a plateau level which was directly related to the dose infused. However, for each dose, the level was much lower in CA than in WA rats. In both WA and CA rats the increase in O2 consumption above the preinfusion rate was linearly related to the increase in the concentration of plasma NA, but the increase in O2 consumption with each dose was greater in CA than in WA rats. Thus, the slope of the relation between increase in O2 consumption and increase in plasma NA was greater by 4.7 times in CA than in WA rats. Differences in calorigenic response to circulating NA are attributed to a greater amount of brown adipose tissue (BAT) and to a higher calorigenic capacity per gram of this tissue in CA that in WA rats. The molar concentrations of circulating NA which stimulated calorigenesis in the intact white rat are in the same range (from 10−9 to 10−7 M) as those reported by others to stimulate O2 consumption of isolated hamster brown adipocytes and of perifused rat BAT fragments. It is suggested that circulating levels of NA which are effective in stimulating calorigenesis in the intact animal approximate average synaptic concentrations of NA in calorigenic effectors during noradrenergic nerve stimulation resulting from cold exposure.
Effects of pulmonary stretch receptor afferent stimulation on sympathetic preganglionic neuron firing
Authors: Gerber Urs , Polosa Canio
Published: April 2011

The response of 47 sympathetic preganglionic neurons (SPNs) of the cervical nerve to activation of pulmonary stretch receptors has been studied in Nembutal-anaesthetized. paralyzed, thoracotomized, artificially ventilated cats. The discharge of 62% of the SPNs was depressed by lung inflation or by electrical stimulation of the lowest threshold afferent fibers in the vagus nerve. The SPNs which were most sensitive to these manoeuvers were those whose discharge had an inspiration-synchronous component. All the SPNs of this type tested were depressed. Their response paralleled that of phrenic motoneurons. The SPNs which were least sensitive to these manoeuvers were those whose firing pattern showed no respiratory modulation. Only 12% of the SPNs of this type tested were depressed. In some SPNs, selective suppression of inspiration-synchronous activity by hypocapnia revealed a residual firing which could not be altered by pulmonary stretch receptor afferent activation. For comparison, the reflex response of the same sample of SPNs to the systemic arterial pressure increase caused by intravenous injection of noradrenaline (5 μg/kg) was studied. The discharge of 85% of the SPNs was depressed during the pressor effect of noradrenaline. The frequency of occurrence of depressant effects was similar in respiratory-modulated and nonmodulated SPNs. Also depressed was the residual discharge in hypocapnia of respiratory-modulated SPNs. Thus, the distribution in the SPN pool of the depression evoked by a systemic arterial pressure rise contrasts with that caused by activation of pulmonary stretch receptor afferents. These results provide a direct demonstration of the depressant action of pulmonary stretch receptor afferents on SPNs, an action that had previously been hypothesized on the basis of indirect evidence. The observation that activation of these afferents depresses mainly the inspiration-synchronous component of SPN firing suggests that the effect is predominantly relayed to the SPN pool via the respiratory center.
The metabolic pattern of spontaneously released [3H]norepinephrine in the presence of uptake inhibitors
Authors: Jayasundar S. , Vohra M. M.
Published: April 2011

The effect of uptake inhibitors on the spontaneous release of [3H]norepinephrine was studied using rat isolated vas deferens. Cocaine, desmethylimipramine, phenoxybenzamine, and guanethidine caused an increase in the spontaneous outflow of tritium, but did not alter the metabolic pattern of released [3H]norepinephrine. Bretylium caused an increase of both total tritium outflow and norepinephrine content. It is suggested that these drugs caused release of norepinephrine from storage sites and that norepinephrine was metabolized within the nerve terminals before reaching the biophase.
Effects of anesthetics on diphenylhydantoin metabolism in the rat: possible inhibition by diethyl ether
Authors: Umeda T. , Inaba T.
Published: April 2011

The effects of diethyl ether and urethane on the elimination of diphenylhydantoin (DPH) in the rat were compared. The apparent half-life of DPH following a dose of 10 mg/kg, iv, under continuous ether anesthesia was 284 ± 47 min, while the half-life under urethane anesthesia was 25.5 ± 6.3 min. The latter was in agreement with the literature value for DPH half-life without anesthesia. The effects of both anesthetic agents on bile flow and indocyanine green clearance were not different. Following intravenous administration of DPH (1 mg/kg), DPH metabolites excreted in bile at 2 h were 75.3 ± 4.8% of the dose with urethane anesthesia and 25.0 ± 5.0% of the dose with continuous ether anesthesia. The data suggest that ether may inhibit the DPH metabolism in vivo, most likely at the hydroxylation step, while urethane does not.
Effects of phenytoin on acetylcholinesterase activity and cell protein in cultured chick embryonic skeletal muscle
Authors: Cisson C. Michael , Entrikin Richard K. , Wilson Barry W.
Published: April 2011

Cultured pectoral muscle from 11-day-old chick embryos was treated for 48 h with phenytoin (diphenylhydantoin, DPH) in concentrations ranging from 15 to 270 μg/ml on days 7–9 in vitro. Acetylcholinesterase (AChE, EC 3.1.1.7), creatine phosphokinase (CPK, EC 2.7.3.2), and lactic dehydrogenase (LDH, EC 1.1.1.27) activities, [3H]leucine incorporation into protein, and total protein of the cultures decreased in a dose-related manner with DPH concentrations of 30 μg/ml and greater. Total AChE activity and AChE activity released into the medium were specifically decreased with 15 μg DPH per millilitre. In cultures treated chronically with 15 μg DPH per millilitre on days 5–13 in vitro, total AChE activity and AChE activity released into the medium were 66.0 ± 13.2 and 64.7 ± 11.8% of untreated controls, respectively, but cellular AChE activity, cell protein, and [3H]leucine incorporation into protein were unaffected. The results indicate that DPH specifically decreases the total net synthesis of AChE activity by a direct action on cultured chick embryo muscle.
45Ca displacement related to pharmacologically induced prolonged action potentials in Nitella flexilis
Authors: Netten C. van , Belton P.
Published: April 2011

Nitella cells were loaded with 45Ca2+ to an activity of 2 × 105 cpm. Insertion of two glass-capillary electrodes into each of six cells released varying amounts of Ca2+ in the order of 1 μmol per cell, but hyperpolarizing and depolarizing pulses up to 500 ms in duration caused no measurable loss (< 57 pmol) of Ca2+ even when the latter elicited action potentials. Addition of 10 μmol of Ba2+ or tetraethylammonium (TEA) caused losses up to 1200 pmol of Ca2+ from the cells and prolonged the action potentials by a factor of three or more. Subsequent addition of Ba2+ or TEA to treated cells caused no further losses of Ca. Because prolonged action potentials can apparently only be elicited after the chelation or displacement of Ca2+, we propose that, as in many animal cells, the K+ channels responsible for the normal brief repolarizing phase of the action potential are controlled by Ca2+ in these electrically excitable plant cells.
Disopyramide phosphate: is it just another quinidine
Authors: Kus Teresa , Sasyniuk Betty I.
Published: April 2011

We compared the effects of a therapeutic concentration of disopyramide with those of quinidine and lidocaine on the action potential characteristics and on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential in the same normal Purkinje fiber in which constant impalement was maintained for more than 7 h. All the drugs depressed the steady-state upstroke velocity in the following order of magnitude: quinidine > disopyramide > lidocaine. Both lidocaine and disopyramide shifted the normalized steady-state curve to more negative membrane potentials indicating a greater depression of upstroke velocity at lower membrane potentials. Quinidine did not shift this curve. Lidocaine abbreviated all phases of repolarization while both disopyramide and quinidine shortened the plateau phase and lengthened the terminal phase of the action potential. The results suggest that the actions of disopyramide on upstroke velocity resemble those of lidocaine, while its effects on action potential duration resemble those of quinidine. The actions of this drug are therefore more complex than previously assumed.
Spinal reflexes as a basis for tremor in the premammillary cat
Authors: Nichols T. R. , Stein R. B. , Bawa P.
Published: April 2011

A maintained tremor observed in premammillary cats has been studied by varying the load attached to the soleus muscle, by electrical recording, and stimulation. The frequency and amplitude of the tremor varies widely with changes in elastic or inertial loading (springs or flywheels). These variations agree well with predictions based on the idea that the tremor is maintained by reflexes reinforcing a tendency for oscillation in a mass-spring system (which includes the elasticity of the muscle). Spinal stretch reflexes are probably responsible since a relatively fixed delay of 8.5 ± 2.9 ms is observed between the peaks of recorded afferent and electromyographic activity. Stimulation of the lateral gastrocnemius – soleus nerve completely resets the tremor, again suggesting a reflex origin.
Zinc, cadmium, and iron interactions during intestinal absorption in iron-deficient mice
Authors: Hamilton D. L. , Bellamy J. E. C. , Valberg J. D. , Valberg L. S.
Published: April 2011

Zinc absorption from a test dose of (65Zn) zinc chloride was increased in mice with a high capacity to absorb iron induced by a low-iron diet. When radiolabelled zinc chloride in concentrations varying from 0.025 to 0.30 mM was perfused through open-ended duodenal loops of mice fed this diet, the proportion of zinc taken up from the lumen and transferred to the body was greater from lower than from higher doses. The addition of iron to the perfusate inhibited zinc uptake and transfer, and zinc had a similar effect on iron absorption. Cadmium, a potent inhibitor of iron uptake in mice fed a low-iron diet, impaired zinc uptake under these dietary conditions. These results suggest that in dietary-induced iron deficiency there are analogous mucosal binding sites for the uptake of iron and zinc. There also appear to be mutually exclusive binding sites for the absorption of these metals: radiolabeled iron absorption from an intragastric test dose was enhanced in mice with a high capacity to absorb iron produced by bleeding, whereas the absorption of zinc was not increased.
An investigation of the activity of opiate drug receptors located on frog skeletal muscle fibre membrane
Authors: Frank G. B. , Marwaha J.
Published: April 2011

Extracellular and intracellular microelcctrode studies were conducted to test the actions and interactions of opiate agonists, antagonists, and procaine on action potentials in frog sartorius muscles. Extracellular studies showed that morphine, methadone, propoxyphene, and procaine all depressed action potential production. Low concentrations of naloxone or naltrexone antagonized the excitability depression produced by the three opiate agonists but not the depression produced by procaine. Intracellular studies revealed that certain concentrations of the opiate agonists produced a biphasic decline in the stimulus-induced increase in sodium conductance (gNa). Naloxone or naltrexone antagonized only the second phase of this decline. These results show that part of the excitability depression produced by opiate agonists is due to an action on opiate drug receptors.
A radiotracer method for the measurement of central nervous system catecholamines in vivo
Authors: Tang S. W. , Stancer H. C. , Warsh J. J.
Published: April 2011

A new strategy for measurement of brain catecholamines was tested in an animal model. [3H]Norepinephrine was infused intravenously in rabbits to label the peripheral norepinephrine pools. The specific activity of urinary 3-methoxy-4-hydroxymandelic acid was consistently higher than that for 3-methoxy-4-hydroxyphenylglycol (MHPG). Central sympathectomy with 6-hydroxydopamine abolished this difference. Using the formula we propose, it is estimated that 30–50% of urinary MHPG originates from the central nervous system.
The effect of acid–base changes on skeletal muscle twitch tension
Authors: Fretthold David W. , Garg Lal C.
Published: April 2011

The effects of acid–base alterations produced by changing bicarbonate (metabolic type), carbon dioxide tension (respiratory type), or both bicarbonate and carbon dioxide tension (compensated type) on skeletal muscle twitch tension, intracellular pH, and intracellular potassium were studied in vitro. Hemidiaphragm muscles from normal rats and rats fed a potassium-deficient diet were used. Decreasing the extracellular pH by decreasing bicarbonate or increasing CO2 in the bathing fluid produced a decrease in intracellular pH, intracellular K+, and muscle twitch tension. However, at a constant extracellular pH, an increase in CO2 (compensated by an increase in bicarbonate) produced an increase in intracellular K+ and twitch tension in spite of a decrease in intracellular pH. The effect on twitch tension of the hemidiaphragms showed a rapid onset, was reversible, persisted until the buffer composition was changed, and was independent of synaptic transmission.It is concluded that the twitch tension of the skeletal muscle decreases with a decrease in intracellular K+. The muscle tension also decreases with an increase in the ratio of intracellular and extracellular H+ concentration. However, there is no consistent relationship between muscle tension and extracellular or intracellular pH. The muscle tension of the diaphragms taken from K+-deficient rats is more sensitive to variations in CO2, pH, and bicarbonate concentration of the medium than that of the control rat diaphragms.
Cholesteryl ester depletion from the ovaries of superovulated female rats fed a normal or essential fatty acid deficient diet
Authors: Young Angela K. , Walker Brian L.
Published: April 2011

The cholesteryl ester content of the ovaries was determined in rats fed diets containing corn oil or hydrogenated coconut oil (essential fatty acid (EFA) deficient) and subjected to superovulation by injection of luteinizing hormone and follicle-stimulating hormone. Superovulation increased ovarian weight; the effect was greater in animals fed corn oil. Superovulation significantly decreased total ovarian cholesteryl ester concentration in animals fed corn oil, with disproportionately large decreases occurring in the esters of 20:1, 20:2, 22:5ω6, and 22:6ω3. Significant decreases were observed in these esters when the data were expressed on a unit mass of tissue basis or in relation to total ovarian mass. In superovulated, EFA-deficient rats, esters of 18:1, 20:1, 22:5ω6, and 22:6ω3 were significantly lower per unit mass of tissue but this was due, in all cases except that of 22:6ω3, to the increased mass of ovarian tissue; there was no decrease in total esters per ovary weight during superovulation of deficient rats. The pattern and degree of selective changes in ovarian cholesteryl esters during superovulation were different from those previously reported for adrenal esters of stresssd rats.
Absence of Na+–H+ barrier function in mucosa of canine small bowel
Authors: Kelly Darlene G. , Code Charles F.
Published: April 2011

The study was designed to determine whether the special Na+–H+ barrier function or the gastric mucosa is present in the mucosa of the small bowel and whether a gastric mucosal barrier breaker (hexanoic acid) would accelerate the fluxes of sodium in duodenum–jejunum and ileum as in the stomach. The observations were made in healthy conscious dogs with Thiry-Vella fistulae of the small bowel or Heidenhain pouches of the gastric corpus. These barrier characteristics of the stomach were completely absent in the small intestine where bidirectional Na fluxes were 5–10 times greater than in the stomach and were not accelerated by hexanoic acid as they were in the stomach.A comparison was made between the rates of absorption of hexanoic acid, sodium hexanoate, and HCl from the pouches and fistulae. The lipid-soluble fatty acid was transported at all sites more rapidly than its water-soluble sodium salt. In the stomach and ileum the H+ of HCl and sodium hexanoate were absorbed at similar slow rates. The duodenal–jejunal mucosa, however, transported H+ at rates nearly identical to those of hexanoic acid. In our tests HCl was not neutralized in duodenal contents while large quantities were neutralized in the contents of ileum.
Acute tolerance to ethanol on the release of acetylcholine from the cat cerebral cortex
Authors: Sinclair J. G. , Lo G. F.
Published: April 2011

Ethanol (1 g/kg, iv) produced a peak depression of acetylcholine release from the cat sensorimotor cortices within 30 min of the ethanol administration but recovery to control levels occurred in the following 30 min. However, the concentrations of ethanol in the blood and in the solution bathing the cortex remained stable during this recovery period. This example of acute tolerance to ethanol is possibly related to the well-known acute tolerance that develops to the behavioural effects of ethanol.
Chronotropic and inotropic effects of neurotensin on spontaneously beating auricles
Authors: Quirion R. , Rioux F. , Regoli D.
Published: April 2011

Synthetic neurotensin (NT) was shown to exert a potent positive inotropic and chronotropic action in spontaneously beating guinea pig and rat auricles and to be inactive in the rabbit auricles. The positive inotropic effects of NT in guinea pig and rat auricles were detected at concentrations as low as 3.0–6.0 × 10−10 M. Maximal concentrations of NT (3.1 × 10−7 M) increased the amplitude of contractions by 135 and 55% in guinea pig and rat auricles, respectively. On the basis of ED50 values, NT was found to be 20–30 times more potent than epinephrine in increasing the force of contraction in guinea pig and rat auricles. The results suggested that the positive inotropic and chronotropic actions of NT are species dependent. The potential usefulness of NT in the treatment of experimentally induced heart failure is underlined.
Effects of morphine, naloxone, d,l-cyclazocine, and d-amphetamine on behaviour controlled by a schedule of interresponse time reinforcement
Authors: Adam-Carrière Dyane , Merali Z. , Stretch Roger
Published: April 2011

The separate effects of graded doses of morphine, naloxone, d,l-cyclazocine, and d-amphetamine on responding maintained by a differential reinforcement of low rate schedule of food presentation were examined in rats. Morphine did not alter response rates at doses of 1–5.6 mg/kg; at 10 mg/kg a 57% decrease in responding was observed and behaviour was even more severely depressed by 30 mg of morphine per kilogram. Naloxone did not affect responding at doses ranging from 0.1 to 10 mg/kg. d,l-Cyclazocine at doses of 3 and 5.6 mg/kg induced substantial increases in responding not observed when the dose was increased to 10 mg/kg. Cyclazocine, as well as morphine, produced dose-dependent decreases in the number of reinforcements per session. d-Amphetamine exerted a biphasic effect on responding; small doses increased response rates (0.3–3 mg/kg) and responding was suppressed by the drug at a dose of 10 mg/kg. Behaviourally active doses of d-amphetamine caused a dose-dependent reduction in the number of reinforcements per session. Naloxone at otherwise inactive doses (1–10 mg/kg) was found, in separate experiments, to antagonize the rate-decreasing effects of morphine, and to reduce the rate-increasing effects of d-amphetamine. The latter effect is not easily interpreted but confirms and extends other research employing rats in which naloxone was found to reduce the rate-increasing effects of small doses of d-amphetamine upon locomotor activity and responding maintained by a continuous electric-shock postponement procedure.In additional experiments morphine was given daily for 25 consecutive sessions at a dose of 30 mg/kg, 5 min preceding each test session. Responding was suppressed throughout this period and the dose of morphine given before each session was reduced to 10 mg/kg for 35 further sessions. Tolerance to the rate-decreasing effects of morphine was demonstrated; naloxone given in conjunction with morphine (10 mg/kg) in morphine-tolerant rats restored to control values the number of reinforcements per session without causing significant change in overall rates of responding. Few experiments have dealt previously with the development of tolerance to the behavioural effects of morphine under comparable dose regimens, time-course relationships, or behavioural testing procedures. Systematic analyses of these interrelated variables are needed since it is now evident that the schedule employed to maintain responding itself exerts significant effects.
Antinociceptive effects of intrathecally administered human β-endorphin in the rat and cat
Authors: Yaksh Tony L. , Henry James L.
Published: April 2011

Rats chronically implanted with intrathecal catheters displayed a dose-dependent increase in the hot-plate and tail-flick response latencies following the injection of human β-endorphin into the lumbar spinal subarachnoid space through the indwelling catheter. β-Endorphin was approximately 25 times more potent than morphine on a molar basis. Matching morphine and β-endorphin doses such that approximately equal submaximal effects occurred, it was observed that the antinociception produced by β-endorphin lasted approximately three times longer than that produced by morphine. Experiments with intrathecal injection of β-endorphin into the spinal subarachnoid space of cats fitted with intrathecal catheters also revealed a potent antinociceptive effect which was completely antagonized by naloxone. In the rats, naloxone administered systemically in doses of 10–100 μg/kg produced a parallel shift in the dose–response curves of both nociceptive measures suggesting a competitive antagonism. Using a dose ratio analysis, an in vivo pA2 of 7.1 for naloxone was obtained. These data and those derived from previous work based on the pA2 suggest that the interaction of morphine, certain pentapeptides, and β-endorphin is the same with regard to the spinal opiate receptor population mediating behavioraily defined analgesia.
Pharmacological studies on the pulmonary vein of the horse. I. Effects of selected spasmogens
Authors: Hanna C. J. , Eyre P.
Published: April 2011

Horses suffer from a respiratory condition, similar to human allergic asthma, that is characterized by severe dyspnea, wheezing, coughing, and mucus production. Mediator substances released during the allergic reaction may contract airways and pulmonary vasculature. Nothing is known of the effects of autacoids and other vasoactive substances on equine pulmonary vessels. Therefore, spiral strips of equine pulmonary vein were prepared in vitro and the effects of histamine (H), 5-hydroxytryptamine (5HT), bradykinin (Bk), carbachol (Carb), and phenylephrine (Phen) were studied. The order of contractile effectiveness for the agonists on the vein was found to be 5HT > H> Bk > Phen > Carb, although H consistently produced the greatest maximal effects. H1-receptors appeared to mediate H contractions while H2-receptors had no measurable effect. 5HT responses were mediated directly by 'D-type' smooth muscle receptors. Bk produced contractions but of a lesser magnitude than either H or 5HT. Varying degrees of tachyphylaxis were observed for each agent. α-Adrenergic receptor stimulation by Phen initiated low-magnitude contractions whereas Carb exhibited virtually no activity on the pulmonary vein. Contractile responses of pulmonary veins to various spasmogens may contribute to the equine asthmatic response by raising vascular hydrostatic pressure, thereby enhancing edema formation.