bluuebunny/crossref_metadata_2025 huggingface dataset:
Asialoglycoprotein clearance in the chicken: evidence for the lack of a hepatic asialoglycoprotein receptor
Authors: Regoeczi E. , Hatton M. W. C.
Published: April 2011

The behaviour of desialylated human and chicken acid α1-glycoproteins is reported in chickens. Although desialylation resulted in accelerated disappearance rates from the plasma of both proteins, nevertheless the asialoproteins were eliminated much more slowly than expected on the basis of earlier observations in mammals. Analysis of tissue radioactivities, including kidney, liver, lung and spleen, failed to demonstrate any accumulation of the labeled asialoproteins in the liver, which is contrary to the situation in mammals. The main pathway for the elimination of desialylated human acid α1-glycoprotein in the chicken is via the kidney (tubular catabolism and/or urinary excretion). The clearance of desialylated chicken acid α1-glycoprotein is more complex as it involves the kidney as well as the reticuloendothelial system.These findings indicate that, unlike mammals, chickens do not possess a hepatic plasma membrane receptor for asialoglycoproteins. This raises the possibility that the presence or absence of this specific receptor may constitute a fundamental biological difference between mammals and birds.
Effects on tissue and electrolytes of a mineralocorticoid blocker during DOCA-induced potassium depletion
Authors: Levine David Z. , Sarkar Kiriti
Published: April 2011

Chronic experiments were carried out on three groups of rats to evaluate tissue and electrolyte effects of a mineralocorticoid blocker canrenoate potassium (SC-14266) during DOCA-induced hypokalemic metabolic alkalosis. Group I animals received DOCA alone, group II received DOCA plus canrenoate, while group III received canrenoate alone. The daily dose ratio (per kilogram of body weight) was 180 mg canrenoate – 0.45 mg DOCA. All animals ate a synthetic diet and drank 0.15 N NaHCO3 Group II animals demonstrated a lesser degree of metabolic alkalosis and a higher muscle potassium content when compared with group I rats. The most conspicuous histological abnormality was myocardial necrosis, the degree and extent of which was impressively reduced by the blocking agent.
The influence of acute diazepam pretreatment on the action and disposition of [14C]pentobarbital in rats
Authors: Repentigny L. de , Hanasono G. K. , Plaa G. L.
Published: April 2011

Diazepam (DZP) pretreatment (100 mg/kg, ip) of rats 6 h before pentobarbital administration (45 mg/kg, ip) prolonged the barbiturate-induced narcosis. The concentrations of [14C]pentobarbital and total pentobarbital derivatives in blood or brain showed no differences between control and DZP-pretreated animals. The brain and blood concentrations of pentobarbital, when measured at a time corresponding to the respective arousal times from pentobarbital narcosis, were lower in the DZP-pretreated group. These results indicate that acute DZP pretreatment increases the sensitivity of the rat brain to pentobarbital rather than inducing changes in the disposition of the barbiturate.
Effect of adrenaline on sugar transport in the perifused left atrium
Authors: Bihler I. , Sawh P. C.
Published: April 2011

The effect of adrenaline on the membrane transport of 3-methylglucose was studied in perifused isolated rat left atria that had been fully arrested. In this preparation a high concentration of adrenaline stimulated and a low one decreased sugar transport. The stimulatory effect was strongly inhibited by the β-adrenergic blocker propranolol and by the antilipolytic agent nicotinic acid. As the atria were not beating, the effects were not mediated by changes in the rate or strength of muscular contraction. The possible mechanisms of these effects of adrenaline on sugar transport are discussed.
Phenobarbitone-induced urinary excretions of D-glucaric acid and 6β-hydroxycortisol in man
Authors: Latham A. N. , Turner P. , Franklin C. , Maclay W.
Published: April 2011

The urinary excretions of D-glucaric acid and 6β-hydroxycortisol were determined in normal subjects before, during, and after 14 days treatment with placebo or phenobarbitone. The excretion of both metabolites was significantly potentiated by phenobarbitone and returned to baseline values 1 month after treatment was withdrawn. It was suggested that the determination of urinary D-glucaric acid reflects the activity of the hepatic microsomal mixed function oxidase system after the administration of an inducing agent such as phenobarbitone.
The effects of AMP on the potential of rat cerebral cortical neurones
Authors: Edstrom J. P. , Phillis J. W.
Published: April 2011

Intracellular recordings have shown that AMP, applied extracellularly, consistently produces a hyperpolarization in the absence of any pronounced alterations in membrane conductance and causes a reduction in spontaneously occurring and evoked postsynaptic potentials. Potential mechanisms of action of AMP are discussed, including the possibility that it may depress transmitter release from presynaptic nerve terminals.
Reduced hemoglobin affinity for oxygen in venous blood following hemodilution, independent of changes in pH or
Authors: Lautt W. Wayne
Published: April 2011

A rapidly induced and readily reversible shift in the affinity of hemoglobin for oxygen has been demonstrated. The shift, similar to the Bohr effect, is independent of [Formula: see text] or pH changes. It occurred within 30 min of hemodilution and was seen in portal venous blood but not arterial blood. A hypothesis is suggested involving a phasic alteration in levels of 2,3-diphosphoglycerate (DPG) or ATP binding to hemoglobin. It is proposed that, following hemodilution, the degree of binding of these phosphates to hemoglobin increases on passage through the intestinal vascular bed. The increased DPG binding to hemoglobin results in displacement of additional oxygen. As the blood becomes reoxygen-ated, the levels of DPG-hemoglobin binding decline and DPG is displaced from the hemoglobin by oxygen.
Arterial bifurcation flows – effects of flow rate and area ratio
Authors: Feuerstein I. A. , Masry O. A. El , Round G.
Published: April 2011

Velocity profiles and surface shear rates, for three model symmetrical bifurcations made of glass from dimensions based on the arterial system, were investigated. The models studied had area ratios of 0.75, 1.02, and 1.29, with a common included angle of 75°. Area ratio and parent tube flow rate were the two independent variables evaluated. Measurements were made with a tracer particle technique using cinephotography. Velocity profiles had their highest values on the inside, and lowest values on the outside, of the branch. Flow symmetry existed in the plane perpendicular to the plane of the bifurcation. Surface shear rates remained well above the daughter-tube developed values, between two and six diameters downstream from the carina. Shear rates below the daughter-tube developed value were found on the outside wall between the carina and two daughter-tube diameters downstream. Vortex-like flow was absent in this region for the 0.75 area ratio branch and was found above 900 Reynolds number in the 1.29 area ratio branch. The disturbed flow described by others in this region may not contain vortex-like streamlines for the physiologically important 0.75 area ratio.
Dispersed cell cultures of the rat pineal: growth and morphological differentiation
Authors: Wilkinson Michael
Published: April 2011

A method is described for the preparation and growth of rat pineal monolayer cultures derived from both mature and immature animals. The cultures were observed to undergo profound but reversible morphological differentiations by addition of dibutyryl-cAMP, monobutyryl-cAMP, papaverine, prostaglandins, and adenosine, and by removal of serum. Sodium butyrate and theophylline had no effect. Time-lapse photography indicated that this reversible transformation took place via a contraction-relaxation mechanism. Both colcemid and cytochalasin B inhibited the transformation. These results demonstrate that this type of morphological transformation, previously demonstrated in tumour and embryonic cell cultures, can also occur in nonembryonic, non-neoplastic tissue, and may be related to a general dedifferentiative process occurring in monolayer cultures.
Binding of anticonvulsant drugs to cytochrome P-450: correlation with evidence of induction of hepatic microsomal enzymes
Authors: Latham A. N. , Sweeney G. D.
Published: April 2011

Mephenytoin, diphenylhydantoin, pheneturide, and phenobarbital produced a concentration-dependent inhibition in the binding of hexobarbital to cytochrome P-450 at the type 1 site, while sulthiame slightly potentiated, and ethosuximide did not affect the binding characteristics of hexobarbital. Diphenylhydantoin, phenobarbital, and pheneturide have previously been shown to enhance the urinary excretion of D-glucaric acid (DGA), while sulthiame inhibited the potentiation of DGA excretion caused by these drugs, and ethosuximide produced no change. The results suggest a close relationship between the ability of these drugs to induce hepatic microsomal drug-metabolizing enzyme systems (as indicated by enhancement of DGA excretion) and binding behaviour at the type 1 site.
Effect of adrenaline on insulin secretion in rats treated chronically with adrenaline
Authors: Rousseau-Migneron Suzanne , Nadeau André , LeBlanc Jacques
Published: April 2011

To determine whether rats could adapt to a chronic exogenous supply of adrenaline by a decrease in the well-known inhibitory effect of adrenaline on insulin secretion, plasma glucose and insulin levels were measured in unanesthetized control and adrenaline-treated rats (300 μg/kg twice a day for 28 days) during an adrenaline infusion (0.75 μg kg−1 min−1), after an acute glucose load (0.5 g/kg), and during the simultaneous administration of both agents. Chronic treatment with adrenaline did not modify the initial glucose levels but it greatly diminished the basal insulin values (21.57 ± 2.48 vs. 44.69 ± 3.3 μU/ml, p < 0.01). In the control rats, despite the elevated glucose concentrations, a significant drop in plasma insulin levels was observed within the first 15 min of adrenaline infusion, followed by a period of recovery. In the adrenaline-treated group, in which plasma glucose levels were lower than in control animals, plasma insulin levels did not drop as in control rats, but a significant increase was found after 30 min of infusion. During the intravenous glucose tolerance test, the plasma glucose and insulin responses showed similar patterns; however, during the concomitant adrenaline infusion, the treated rats showed a better glucose tolerance than their controls. These results indicate that rats chronically treated with adrenaline adapt to the diabetogenic effect of an infusion of adrenaline by having a lower inhibition of insulin release, although the lower basal insulin levels may indicate a greater sensitivity to endogenous insulin.
Effect of alterations in ambient temperature on blood flow in the skin
Authors: Grayson J. , Livingstone S. D.
Published: April 2011

The effect of changing ambient temperature on skin temperature was recorded in human subjects; also, its effect on blood flow was measured using venous occlusion and optical plethysmography. When cold stimulus was removed in stages using a heating cabinet, it was found that a biphasic flow response occurred in the fingers with each step change in temperature. There was a rapid transient rise followed by a decline to an equilibrium flow level. The transient rise occurred even when the temperature rose from 37 to 40 °C, although at this level the equilibrium remained unchanged. It is suggested that the transient rise was due to stimulation of Hensel's dynamic warmth receptors, whereas the rise in equilibrium temperature was due to removal of cold stimulus, which at low ambient temperatures maintains reflex vasoconstriction through activation of static cold receptors. Upper arm skin responded to removal of cold stimulus by a fall in temperature. Immersion of a different limb in cold water produced vasoconstriction in fingers but vasodilatation in the upper arm skin. It is suggested that this may be due to neurogenic vasodilatation, though the present work gives no indication as to pathways.
Characterization of the neuromuscular block produced by clindamycin and lincomycin
Authors: Wright J. M. , Collier B.
Published: April 2011

The site of neuromuscular blockade induced by clindamycin and lincomycin was studied on isolated nerve and nerve–muscle preparations. Clindamycin (3.6 × 10−3 M) but not lincomycin (up to 1.5 × 10−2 M) had a local anaesthetic effect on a frog desheathed nerve preparation. Clindamycin (8 × 10−4 M) and lincomycin (4 × 10−3 M) depressed the response of the rat diaphragm to nerve stimulation and to direct muscle stimulation in parallel. This indicated that the predominant neuromuscular blocking effect of these antibiotics was due to an effect on the muscle. Clindamycin was fivefold more potent than lincomycin in this effect, and the unionized form of both drugs was the active form. Lincomycin (4 × 10−3 M) but not clindamycin (8 × 10−4 M) also had some depressant effect on nerve–muscle transmission as indicated by the interaction of the effects of the antibiotics and d-tubocurarine. The significance of these findings is discussed in relation to the acute clinical toxicity of these antibiotics.
Ca2+-dependence of the evoked release from guinea pig cerebral cortex slices of endogenous 14C-labelled amino acids, labelled via D-[U-14C]glucose
Authors: Potashner S. J.
Published: April 2011

Spontaneous and electrically evoked release of exogenous labelled amino acids and endogenous amino acids labelled from D-[U-14C]glucose were compared in control and Ca2+-free medium using guinea pig cerebral cortex slices. Spontaneous release of all labelled amino acids, except that of endogenous 14C-labelled threonine–serine–glutamine (unseparated) and exogenous [14C]aspartate, was doubled in Ca2+-free medium. The major portion of the electrically evoked release of endogenous [14C]glutamate, [14C]aspartate, γ-amino[14C]butyrate (14C-labelled GABA) and exogenous 3H-labelled GABA was Ca2+-dependent. More than half of the evoked release of the other labelled amino acids was Ca2+-independent. As the pattern of Ca2+-dependence of the evoked releases concurred with the selectivity of the evoked release for endogenous [14C]-glutamate, [14C]aspartate, and 14C-labelled GABA, it was concluded that these labelled amino acids were probably released from the amino acid 'transmitter pool'.
Electronic measurement of red cell flow in micropipettes
Authors: Johannsson P. W. , Jay A. W. L. , Rowlands S.
Published: April 2011

The velocity of human erythrocytes in flow-through tubes of diameter less than 5 μm is measured as a function of driving pressure. The electrical resistance in the lumen of the tube increases when a cell is present, so a pulse can be generated of length inversely proportional to velocity. In the apparatus described the pulses and driving pressure are fed to a computer which derives the correlation between pressure and velocity. Experiments confirm that the resistance to flow of erythrocytes in a narrow tube is substantially the same as that of the suspending medium. The apparatus is being used to study the effects of changes in erythrocyte deformability on flow.
Cerebellar cAMP levels following acute and chronic morphine administration
Authors: Charalampous K. D. , Askew William E.
Published: April 2011

Acute administration of morphine sulfate at 20 mg/kg decreased mouse cerebellar adenosine 3′,5′-cyclic phosphate (cAMP) levels while not affecting cAMP phosphodiesterase (EC 3.1.4.17). The cAMP levels and cAMP phosphodiesterase activities were not affected by chronic treatment. However, cAMP levels increased during abrupt withdrawal both with and without naloxone precipitation, with cAMP phosphodiesterase activities being correspondingly decreased. Propanolol prevented the cAMP increase during abrupt withdrawal.
A progressive and cumulative suppression of the activity of spinal neurones in the nonspinal rat
Authors: MacDonald J. F. , Pearson J. A.
Published: April 2011

Electrical stimulation of the skin of the hindpaw of the rat, at frequencies ranging from 2 to 0.2 s−1, halted the tonic or evoked activity of spinal neurones. The duration of this effect increased with each successive stimulus until it outlasted the interstimulus interval. Tonic activity did not return immediately following termination of the stimulation, and activity was often depressed for periods of up to 5 min. Neurones displaying this behaviour were found in laminae 1 and 4–7 of the cord. Some neurones failed to demonstrate this behaviour following the administration of strychnine. This phenomenon provides a possible substrate for habituation of the flexor reflex that occurs with repetitive and noxious stimulation of the skin.
Metergoline as a selective 5-hydroxytryptamine antagonist in the cerebral cortex
Authors: Sastry B. S. R. , Phillis J. W.
Published: April 2011

In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide, and oxygen, the depressant actions on the cerebral cortical neurones of iontophoretically applied 5-hydroxytryptamine (5-HT) but not of noradrenaline, histamine, AMP, Ca2+, and γ-aminobutyric acid were antagonized by metergoline. These observations indicate that metergoline may be a selective 5-HT antagonist in the cerebral cortex.
The effect of clonidine on vascular reactivity to angiotensin, noradrenaline, and vasopressin in conscious rats
Authors: Gaskell Peter , Melnyk Judith
Published: April 2011

The critical opening pressure (COP) of small vessels in the tails of conscious rats was measured by the spectroscopic technique as an index of arteriolar smooth muscle contraction force. In 11 rats acute intramuscular injection of clonidine (15 μg/kg) decreased systolic blood pressure (SBP) and COP by 13.7 ± 1.7 (SEM) and 7.6 ± 1.1 mmHg, respectively, in intact rats but increased SBP by 30.4 ± 2.6 and COP by 25.9 ± 3.5 mmHg in six ganglion-blocked rats. Reactivity of arteriolar muscle was measured as the increase in COP of the vessels in response to intravenous infusion at three or four dose levels of angiotensin II (2–12 ng kg−1 min−1), noradrenaline (30–120 ng kg−1 min−1), or lysine-8-vasopressin (0.085–0.34 mU kg−1 min−1). The dose–response relationship was considered to be essentially linear and increases in COP in clonidine-treated and control rats were compared directly. Acute administration of clonidine (1, 3, or 10 μg/kg, im) decreased vascular reactivity to each of these agents in both the intact and ganglion-blocked rat. For example, in ganglion-blocked rats total increases in COP were as follows: (1) during infusion of angiotensin (8 ng kg−1 min−1), 22.3 ± 1.3 (SEM) mmHg in clonidine-treated rats and 40.3 ± 3.7 in controls (p < 0.01); (2) during infusion of noradrenaline (120 ng kg−1 min−1), 8.4 ± 1.7 mmHg in clonidine-treated rats and 30.0 ± 2.6 in controls (p< 0.001); and (3) during infusion of vasopressin (0.34 mU kg−1 min−1), 24.8 ± 0.3 mmHg in clonidine-treated rats and 47.8 ± 0.9 in controls (p < 0.001). Chronic treatment of rats with clonidine (20 μg kg−1 day−1) for 7 or more days had a similar effect on vascular reactivity. This apparently nonspecific reduction of vascular reactivity could play an important part in the antihypertensive effect of clonidine hydrochloride.
Characteristics of a somatostatin-binding protein
Authors: Ogawa N. , Thompson T. , Friesen H. G.
Published: April 2011

The concentrations of a somatostatin-binding protein, found in the cytosol of a number of rat tissues, are similar in both sexes, and hypophysectomy has little or no effect on the level of binding protein in tissue extracts. On the other hand, streptozotocin-induced diabetes mellitus causes a modest decrease. The somatostatin-binding proteins obtained from extracts of several rat tissues are not only similar in molecular weight but also exhibit a similar isoelectric point and electrophoretic mobility. Agents that block thiol groups or prevent the formation of disulfide bridges markedly decrease the binding of somatostatin to the cytoplasmic protein. Studies using thiol reagents and gel filtration suggest that free thiol groups in somatostatin-binding protein are important for the binding of somatostatin.
Primary afferent depolarization of C fibres in the spinal cord of the cat
Authors: Calvillo O.
Published: April 2011

The excitability of primary afferent terminals of cutaneous C fibres was tested in the spinal cord of decerebrated cats. C fibre terminal excitability was decreased in the spinal state, and increased by conditioning volleys that activated only A fibres of another cutaneous nerve and by stimulating hair mechanically. It is suggested that C fibre input and therefore nociceptive information to the central nervous system is susceptible to presynaptic control by segmental and suprasegmental mechanisms.
Human lymphocyte migration in vitro: Characterization and quantitation of locomotory parameters
Authors: Noble P. B. , Boyarsky A. , Bentley K. C.
Published: April 2011

Using a time-lapse cinephotomicrographic technique, the locomotory paths taken by lymphocytes have been shown to satisfy the requirements for a continuous-time Markov chain analysis consisting of four directional states defined by the four quadrants of a Cartesian plane and state 0 in which the cells are stationary. The important parameters characterizing this path motion are the average time (waiting time) that a cell spends in each state and the state transition probabilities which, using the Markov model, allow the computation of the probability of the cells moving in a given direction. Our results show that lymphocytes moving alone on glass exhibit a random migration pattern.
Voltage control during inward current flow in rat ventricular muscle using a double sucrose gap technique
Authors: Schanne O. F. , Payet M. D. , P.-Ceretti E. Ruiz
Published: April 2011

In rat ventricular muscle, measurements of the membrane potential with microelectrodes during depolarizing voltage steps showed that deviation of the membrane potential from the command signal were never larger than 15 mV during flow of the fast inward current and that voltage control was regained within 15 ms after the beginning of the voltage step. During the flow of the slow inward current, tail currents elicited by interrupting the time course of the slow current at different time intervals returned exponentially to the steady-state level, thus indicating acceptable voltage control. It is concluded that rat ventricular muscle is a rather favorable preparation for voltage-clamp experiments and this is attributed mainly to the geometry of the preparation.
Baroreceptor influence on a spinal cardiovascular reflex
Authors: Lioy Franco , Szeto Peter M.
Published: April 2011

A stretch of the walls of the thoracic aorta, performed in vagotomized cats without obstructing aortic flow, induces increases in heart rate, myocardial contractility, and arterial pressure. These reflex responses are still present after high spinal section. Cats under chloralose–urethane anesthesia were vagotomized and one carotid sinus was isolated and perfused with arterial blood at constant flow. The contralateral carotid sinus nerve and both aortic nerves were sectioned. A stretch of the walls of the thoracic aorta between the 7th and 10th intercostal arteries induced a reflex increase in mean arterial pressure of 29 ± 2 mmHg (mean ± SE). Stepwise increases of carotid sinus pressure (CSP) or electrical stimulation of the carotid sinus nerve induced stepwise decreases of this reflex response. At maximal baroreceptor stimulation (CSP 212 ± 9 mmHg) the reflex response to aortic stretch was reduced by 42%.These experiments show that this spinal cardiovascular reflex is at least partially under the inhibitory control of the baroreceptor input.
Effects of pH on K depolarization and contracture in frog muscles
Authors: Lorković Hrvoje
Published: April 2011

Membrane potential changes and mechanical tension provoked by 20 or 80 mM K at pH 8.0 or 4.5 were measured in muscle fiber bundles from Rana temporaria and Rana esculenta. The bathing solution contained Cl as the main anion. Low pH increased the depolarizing efficiency of high K to about the same degree in muscles of both species of frogs. The tension–[K] relationship was shifted toward lower [K] in muscles from R. temporaria and toward higher [K] in muscles from R. esculenta. It was concluded that the depolarization–contraction coupling was insensitive to pH changes in the former but not in the latter frog species.
The effects of gonadectomy on the hepatic activities of aryl hydrocarbon hydroxylase, epoxide hydratase, and glutathione S-transferase in Wistar rats pretreated with oral methadone∙HCl
Authors: Gontovnick L. S. , Roelofs L. , Bellward G. D.
Published: April 2011

Methadone∙HCl given in the drinking water for 4 weeks increased microsomal epoxide hydratase activity in the liver of adult male Wistar rats, with no change in aryl hydrocarbon hydroxylase activity. In contrast, in female rats it raised aryl hydrocarbon hydroxylase with no change in epoxide hydratase activity. Gonadectomy altered the effect of methadone on epoxide hydratase, but not on aryl hydrocarbon hydroxylase activity, in both sexes. In ovariectomized rats, but not in controls, methadone nearly doubled the epoxide hydratase activity, whereas in male rats castration decreased the inductive effect of methadone. Gonadectomy had a significant effect on the results of methadone treatment with respect to glutathione S-transferase activity in female rats. A sex difference was noted in the control levels of aryl hydrocarbon hydroxylase and glutathione S-transferase, but not of epoxide hydratase activity. The glutathione S-transferase and aryl hydrocarbon hydroxylase activities were decreased in castrated male rats, whereas epoxide hydratase activity was unaltered. It is concluded that sex hormones play an important role in the induction of epoxide hydratase and glutathione S-transferase by methadone, but not of aryl hydrocarbon hydroxylase, at this particular dosage regime.
The effects of Ca2+ antagonists on mechanical responses and Ca2+ movements in guinea pig ileal longitudinal smooth muscle
Authors: Rosenberger Lois B. , Ticku M. K. , Triggle D. J.
Published: April 2011

The Ca2+ antagonists, Mn2+, Co2+, D 600 (α-isopropyl-α-[(N-methyl-N-homoveratryl)-γ-aminopropyl]-3,4,5-trimethoxyphenylacetonitrile), and BAY-1040 (2,6-dimethyl-3,5-dicarbo-methoxy-4-(2-nitro)phenyl-1,4-dihydropyridine) inhibited the response of guinea pig ileal longitudinal muscle to the muscarinic agonist CD (cis-2-methyl-4-dimethylaniinomethyl-1,3-dioxolane methiodide). With the exception of Tm3+ these agents were more effective against the tonic component of response.BAY-1040 was equally effective against phasic components of CD and K+ responses and, although more potent against tonic responses, also failed to discriminate between the tonic components of response to CD and K+. D 600, although less potent than BAY-1040, behaved similarly to BAY-1040 in failing to discriminate between CD and K+ responses. These data suggest that CD and K+ utilize identical, or at least very similar, sources of Ca2+ to sustain excitation-contraction coupling. The tonic component of the CD response showed an apparently cooperative dependence on Ca2+ concentration but D 600 and BAY-1040 behaved as powerful competitive antagonists against Ca2+ in both components of the response to CD (D 600, KI, 1.2 × 10−7 M (phasic), 9.8 × 10−9 M (tonic); BAY-1040, KI,1.8 × 10−8 M (phasic), 4.8 × 10−9 M (tonic)) with potencies similar to those found in other tissues where these agents inhibit membrane Ca2+ currents. The complete additivity of antagonism produced by combination of equieffective concentrations of Tm3+ and D 600 or BAY-1040 indicated that Tm3+ acts at a site distinct from that occupied by D 600 or BAY-1040. In contrast, D 600 and BAY-1040 appear to interact at a common site. No increase in total 45Ca uptake in the presence of 5 × 10−7 M CD could be detected at 0.5 min (phasic component) or 10 min (tonic component) but a significant decrease was found at 5 min and significant increases were found at later times (30 min, 60 min). However, an increase in the 45Ca cellular content, measured after washing in La3+ to remove superficial Ca2+ and to retain cellular Ca2+, could be detected at 0.5 and 10 min in the presence of 5 × 10−7 M CD, in tissues preequilibrated in 46Ca2+ for 60 min. This increase in cellular 46Ca was blocked by atropine, D 600, BAY-1040, and Tm3+ at concentrations that blocked mechanical response. It is concluded that the mechanical responses of guinea pig ileal longitudinal smooth muscle produced by muscarinic agonists or by KCl use Ca2+ that enters through Ca2+ channels similar to those described in other excitable tissues.
Blood dopamine β-hydroxylase activity and noradrenaline levels in the developing white rat
Authors: Behrens W. A. , Lacelle S. , Depocas Florent
Published: April 2011

Dopamine β-hydroxylase (DBH) (3,4-dihydroxyphenylethylamine, ascorbate: oxygen oxidoreductase (β-hydroxylating) (EC 1.14.17.1)) activity in serum of blood obtained by decapitation of white rats at 19, 20, and 21 days in utero, immediately after birth, and postnatally to 70 days, was measured. Noradrenaline (NA) and DBH in plasma from undisturbed, cannulated, postweaning rats were also assayed. During the last few days in utero and the first 2 postnatal days serum DBH activity tripled and then remained elevated during the suckling period. Upon weaning, serum DBH activity declined at first precipitously and then more slowly, until the adult level was reached around 70 days of age. This postweaning decrease in DBH activity was also observed with the cannulated animals. In contrast, plasma NA levels remained low and constant throughout the postweaning period. In suckling rats treated with 6-hydroxydopamine from 2 to 12 days of age, serum DBH activity decreased to less than half its initial value by day 8. It is suggested that the observed changes in serum DBH activity in fetal and postnatal rats reflect ontogenetic changes in sympathetic nerve terminals and that they are probably not correlated with release of NA.
The effect of cold blockade of the medullary chemoreceptors on the CO2 modulation of vascular tone and heart rate
Authors: Hanna Brian D. , Lioy Franco , Polosa Canio
Published: April 2011

We have previously reported that a direct relationship exists between neurogenic vascular tone in the cat hindlimbs and arterial CO2 tension [Formula: see text]. Since this relationship is not appreciably changed by deafferentiation of peripheral chemoreceptors, we have studied the possible role of structures on the ventral surface of the medulla in mediating the CO2 sensitivity of neurogenic tone. The vagosympathetic trunks and the carotid sinus nerves were sectioned bilaterally in cats under sodium pentobarbital anesthesia. The ventral surface of the medulla was perfused with artificial cerebrospinal fluid of physiological [Formula: see text], pH, and temperature. The animals were hyperventilated with different mixtures of CO2 (0, 4, and 10% in O2), so as to change [Formula: see text] from 12.6 ± 1.2 to 57.4 ± 1.8 mmHg (mean ± SE). The perfusion pressure of the hindlimbs, vascularly isolated and perfused at constant flow, was positively correlated with [Formula: see text]. Bilateral chemosensitive areas of the ventral surface of the medulla oblongata (7 mm caudal to the foramen coecum and 3 mm lateral to the midline) were cooled to a temperature of 12 °C by means of small thermodes. This maneuver decreased the heart rate and perfusion pressure present at each level of [Formula: see text] and also the sensitivity of the perfusion pressure to changes in [Formula: see text]. Cold blockade (12 °C) of the rest of the ventral medullary surface induced a further decrease in heart rate and perfusion pressure but not in the slope of the [Formula: see text] – perfusion pressure relation. Similar results were obtained in a group of adrenalectomized animals. These experiments suggest that the medullary areas which mediate the central CO2-sensitivity of respiratory control systems also play a role in cardiovascular control.
Effects of apomorphine on thermoregulatory responses of rats to different ambient temperatures
Authors: Lin M. T. , Chern Y. F. , Wang Zyx , Wang H. S.
Published: April 2011

Either systemic or central administration of apomorphine produced dose-related decreases in rectal temperature at ambient temperatures (Ta) of 8 and 22 °C in rats. At Ta = 8 °C, the hypothermia was brought about by a decrease in metabolic rate (M). At Ta = 22 °C, the hypothermia was due to an increase in mean skin temperature, an increase in respiratory evaporative heat loss (Eres) and a decrease in M. This increased mean skin temperature was due to increased tail and foot skin temperatures. However, at Ta = 29 °C, apomorphine produced increased rectal temperatures due to increased M and decreased Eres. Moreover, the apomorphine-induced hypothermia or hyperthermia was antagonized by either haloperidol or 6-hydroxydopamine, but not by 5,6-dihydroxytryptamine. The data indicate that apomorphine acts on dopamine neurons within brain, with both pre- and post-synaptic sites of action, to influence body temperature.
Hypoglycemia in newborn dogs provokes substantial ACTH but probably not adrenaline secretion
Authors: Cowan John S. , Hetenyi Jr. Geza
Published: April 2011

The objective of this study was to ascertain whether hypoglycemia in newborn dogs provokes either increased ACTH (and glucocorticoid) secretion and (or) increased catecholamine secretion. Insulin-induced hypoglycemia was studied in 36 pups aged 1–11 days (from nine litters) and five adult dogs. The basic design was (i) a 20-min control period, (ii) a 60-min infusion of insulin (10 Mu kg−1 min−1), and (iii) a 40-min recovery period. In 20 pups, seven blood samples were taken at 20-min intervals; glucose (Beckman analyser) and ACTH (adrenal cell suspension bioassay) were determined. Continuous ACTH secretion rates were calculated by a validated single-compartment method. In three of the seven samples glucocorticoids were determined by fluorimetry. In the adults, 17 samples were analysed for the three materials. All 20 pups showed significant rises in ACTH secretion rates, comparable with those seen in the adults. The expected rises in plasma glucocorticoids were also seen. In the remaining 16 pups, small doses (0.25–4 μg/kg) of adrenaline were injected (intravenously) at the end of the insulin infusion. Six additional blood samples were taken during the subsequent 20 min. Even the smallest dose of adrenaline checked or reversed the downward trend in plasma glucose for 10–20 min. Thus in pups, indirect evidence suggests that little if any endogenous adrenaline was being secreted in response to hypoglycemia, despite adult-like ACTH and glucocorticoid secretion.
Effect of acute exercise on tissue free fatty acids in untrained rats
Authors: Oscai Lawrence B.
Published: April 2011

The effects of a single bout of swimming on free fatty acids (FFA) in adipose tissue, heart, skeletal muscle, and serum were examined. Surprisingly, in previously untrained rats, FFA were elevated (P < 0.001) in epididymal, inguinal, and retroperitoneal adipose depots 48 h after a 2-h swim. FFA in the three fat depots returned to resting levels 96 h after exercise. In heart, soleus, and fast-red fibers of the quadriceps, FFA remained elevated (P < 0.01) for as long as 72 h after the 2-h swim. Serum FFA were still elevated (P < 0.001) 96 h after swimming but not after 168 h. These results provide evidence that the rise in FFA is an acute effect of exercise and not a cellular adaptation resulting from daily episodes of lipolysis induced by exercise training. In a separate experiment, involving the adaptive response to endurance exercise, adipocytes from epididymal, inguinal, and retroperitoneal depots were reduced in size (P < 0.001) to approximately the same degree. These results provide evidence that adipocytes from each depot contribute equally in meeting the energy needs of muscle during repeated bouts of endurance exercise.
Diphenylhydantoin: Disposition and effects of administration on hepatic function in guinea pigs
Authors: Lui E. M. K. , Ecobichon D. J.
Published: April 2011

Diphenylhydantoin sodium (phenytoin; DPH) was administered per os to fasted and non-fasted male and female albino guinea pigs either as single doses or as daily doses for 3 consecutive days. Pharmacokinetic studies involved measurement of the serum and alimentary DPH residues by gas–liquid chromatography following solvent extraction. The transit time of barium meal in the alimentary tract was studied by fluoroscopy in both fasted and nonfasted animals. Animals were killed 24 h following three consecutive daily doses of DPH (25 mg/kg body weight) and in vitro measurements of hepatic microsomal p-nitroanisole O-demethylase (OD), aniline hydroxylase (AH), NADPH-cytochrome c reductase (NADPH-CcR), nonspecific carboxylesterase, and UDPglucuronosyltransferase activities were made.Severe toxicity and sedation were observed at doses of 100 and 50 mg/kg body weight, respectively. No overt signs were observed at a dose of 25 mg/kg body weight, this dosage being selected for futher study. The apparent β-phase t0.5 of serum DPH following a single oral dose of 25 mg/kg body weight was approximately 6.5 h in nonfasted guinea pigs. Initial peak serum levels of DPH were observed at 2 h in fasted and nonfasted animals and secondary peak levels were observed at 12 h in nonfasted and at 24 h in fasted animals. There was a good correlation between the rate of DPH absorption, fasting state, and alimentary transit time. In animals receiving 25 mg DPH/kg body weight orally for 3 consecutive days, there was marked induction of hepatic OD, AH, and NADPH-CcR. No changes were observed in nonspecific carboxylesterase or UDPglucuronosyltransferase activities. The major metabolite of DPH, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), was not detected in the tissue in sufficient quantities to exert an influence on monooxygenase activities.
Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin–pancreozymin
Authors: Cailla H. L. , Sarles H. , Singer M. V.
Published: April 2011

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin–pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg−1 h−1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg−1 h−1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg−1 h−1 of CCK and later for 12 and 24 U kg−1 h−1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.
Structure–activity studies of [des-Arg9]-bradykinin on the B1 receptor of the rabbit aorta
Authors: Drouin J.-N. , Gaudreau P. , St-Pierre S. A. , Regoli D.
Published: April 2011

Eight L-alanine analogues of [des-Arg9]-bradykinin and a few other compounds substituted in positions 5 and (or) 8 have been tested on rabbit aortic strips in order to identify the group(s) responsible for binding and (or) stimulation of the B1 receptor. The results obtained with the L-Ala series have shown that the active group is located at the C-terminal end and it is probably Phe8, while the middle part and the N-terminal end of the peptide molecule are primarily involved in binding the agonist to the receptor. An aromatic ring is required in position 8 for activation of receptors, since the elimination of aromaticity (as in [Leu8,des-Arg9]-bradykinin and in [cyclohexylalanine8,des-Arg9]-bradykinin) brings about pure and competitive antagonists. Some compounds exert an angiotensin-iike effect when applied at very high concentrations.
The effect of spironolactone on the arterial water, cation, and norepinephrine contents of control and 'one-kidney-one-clip' hypertensive dogs
Authors: Constantopoulos George , Gutkowska Jolanta , Genest Jacques
Published: April 2011

Spironolactone at 10 mg per kilogram per day was given to control and 'one-kidney-one-clip' hypertensive dogs for 6–7 weeks. Compared with untreated animals the treated animals had a lower arterial water content, a higher arterial, myocardial, and skeletal muscle sodium content, and variable changes in tissue potassium concentrations.
Actions of narcotic analgesics and antagonists on spinal units responding to natural stimulation in the cat
Authors: Calvillo O. , Henry J. L. , Neuman R. S.
Published: April 2011

Morphine and morphine-related agents were applied by microiontophoresis in the lumbar spinal cord of spinal cats to single units classified on the basis of their responses to natural cutaneous or proprioceptive stimulation. Opiate application had a current-dependent depressant effect on the ongoing activities of about one-third of the units tested. This effect was observed in laminae I and IV–VI, but only with units responding to noxious cutaneous stimuli: the nociceptive responses were themselves depressed. Excitatory and inhibitory responses to glutamate and γ-aminobutyric acid, respectively, were also depressed. Intravenous administration of the opiates at doses reported to produce analgesia in the cat also depressed only units responding to noxious cutaneous stimuli, including their nociceptive responses. This depression could be reversed by either the iontophoretic application (100 nA) or the intravenous administration (0.1–0.8 mg/kg) of naloxone. These results are interpreted as further evidence that the analgesic effects of opiates are at least partly due to an action at the spinal level.
Defect in regulation of membrane transport of monosaccharides in dystrophic muscle
Authors: Elbrink J.
Published: April 2011

The penetration of a nonmetabolized glucose analogue, 3-O-methyl-D-glucose, across the plasma membranes of tissues from dystrophic mice and cardiomyopathic (dystrophic) hamsters has been compared with that of normal controls. Under basal conditions the penetration of test sugar was similar in lens and diaphragm of normal and dystrophic 129/ReJ mice. Stimulation of sugar transport by 2,4-dinitrophenol did occur in normal but not in dystrophic diaphragm. A submaximal concentration of insulin had a more variable effect in dystrophic than in normal muscle while a supramaximal concentration of the hormone increased the uptake of the glucose analogue to an equal extent in the two tissues. In the BIO 14.6 strain of cardiomyopathic hamsters, uncoupling of oxidative phosphorylation did not increase sugar transport in extensor digitorum longus muscles, while the normal effect was observed in dystrophic soleus and in both these muscles of the random bred controls. The absence of an effect by a condition simulating anoxia suggests that in dystrophy, certain muscles are unable to accelerate the entry of glucose when this is required.
Bile flow and electrolyte composition of bile associated with maximum bilirubin excretion in sheep
Authors: Barnhart James L. , Upson Dan W.
Published: April 2011

Changes in the composition of bile accompanying the maximum biliary excretion (Emax) of bilirubin were investigated in sheep. Sheep fitted with chronic 'T-tubes' in the common bile duct were infused with taurocholate and bilirubin at various rates. Bile collected during both pre- and post-bilirubin steady-state periods was analyzed for the biliary concentration of electrolytes, bile salts, and bilirubin. Bilirubin Emax was 24.6 μmol/min while bile salt excretion during this period was 103 μmol/min. At Emax bilirubin entry into bile reached a concentration of 16.1 μmol/mL, increased the biliary concentration of sodium, did not change osmolarity of bile, and did not increase bile flow. The data suggest that bilirubin either interacts with mixed micelles in bile or forms molecular aggregates.
Adrenergic presynaptic receptors: Examination of a hypothesis in guinea pig vas deferens
Authors: Kalsner Stanley
Published: April 2011

The hypothesis was examined that phenoxybenzamine enhances both the overflow of noradrenaline and the mechanical response in guinea pig vas deferens by blockade of presynaptic inhibitory receptors located on adrenergic nerve terminals which serve a negative-feedback function. Preparations were stimulated with a constant small number of pulses but at three different frequencies (1, 5, and 15 Hz) and the relative effectiveness of phenoxybenzamine in enhancing overflow assessed. According to the presynaptic receptor hypothesis inhibition of transmitter output should increase with increasing frequency due to increased activation of receptor sites by endogenously released noradrenaline. The antagonist enhanced the overflow of tritium but did so to a similar extent at all three frequencies, regardless of the length of the interval between pulses. Similarly, no evidence for a greater sensitization of the mechanical response by phenoxybenzamine at the higher frequencies was obtained. The conditions of the present experiment were considered optimal for the operation of the negative-feedback system and the results indicate that the physiological relevance of such a system is questionable.
Lipolytic response, cyclic AMP and cyclic GMP accumulation in rat adipocytes stimulated with ACTH: Effect of MtT-F4 tumor and clofibrate treatment
Authors: Gianoulakis C. , Lis M. , Chrétien M.
Published: April 2011

A hyperlipidemia was induced in male Fisher rats by implantation for 31 days of a mammotropic tumor (MtT-F4) which secretes large quantities of ACTH, GH, and prolactin. Following stimulation of isolated adipose tissue cells with ACTH, the lipolytic response and the accumulation of cyclic AMP were higher in cells derived from the rats with the tumor, while the accumulation of cyclic GMP was not different from control adipocytes. Further, when the isolated adipose tissue cells were stimulated with dibutyryl cyclic AMP the lipolytic response was increased to the same extent in both control and tumor-bearing groups. Clofibrate treatment did not alter the increased lipolytic response though it partially decreased the accumulation of cyclic AMP following stimulation by ACTH in adipocytes derived from tumor-bearing rats. However, clofibrate treatment resulted in a significantly greater accumulation of cyclic GMP in fat cells stimulated with ACTH from both control and tumor-bearing rats. Clofibrate in the diet did not alter the levels of GH or prolactin in the control rats nor were the elevated hormone levels of the tumor-bearing rats changed. Thus the adipose tissue cells from fasted rats treated with clofibrate and treatment withdrawn 24 h prior to sacrifice did not exhibit a decrease in the lipolytic response to ACTH. However, the decrease in the accumulation of cyclic AMP and the increase in the accumulation of cyclic GMP observed may suggest an involvement of these nucleotides in the mechanism of action of clofibrate on the adipose tissue.