bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of substrates and hormones on glycogen content of the mouse hemidiaphragm in vitro
Authors: Davidson J. K. , Haist R. E.
Published: April 2011

The effects of various levels of several substrates and hormones on the glycogen content of mouse hemidiaphragm in vitro in the presence and absence of insulin were determined. Pyruvate (0.64 mg/ml) increased glycogen. Acetoacetate (0.16 mg/ml), β-hydroxybutyrate (2.5 mg/ml), and lactate (2.5 mg/ml) increased glycogen only in the presence of glucose and insulin. A mixture of 19 amino acids (0.2 mg/ml of each) had no effect. Growth hormone (100 μg/ml) had no effect in the absence of insulin, but increased glycogen in the presence of glucose and insulin. Prolactin, thyrotrophin, luteinizing hormone, follicle-stimulating hormone, oxytocin, thyroxine, triiodothyronine, cysteine-treated glucagon, adrenocorticotrophic hormone (512 μg/ml), vasopressin (5.25 μg/ml), and Cortisol (16 μg/ml) had no effect. Epinephrine (0.01 μg/ml) and norepinephrine (0.1 μg/ml) had no effect, but epinephrine (0.1 μg/ml) and norepinephrine (1 μg/ml) decreased glycogen content. At physiologic levels of the tested materials, only glucose and insulin altered the glycogen content of mouse hemidiaphragm.
Cardiac output and organ blood flow in warm- and cold-acclimated rats exposed to cold
Authors: Jansky L. , Hart J. S.
Published: April 2011

Cold acclimation increased the cardiac output of unanesthetized rats when measured at 30 °C. After exposure to 9 °C for 70 min cardiac output further increased by 46% in both warm- and cold-acclimated rats. From the changes in the fractional distribution of cardiac output after cold exposure it was shown that the blood flow increased significantly in muscular organs (heart, diaphragm, skeletal muscles) and in the adrenals of warm-acclimated rats. In cold-acclimated rats the blood flow to the brown and white adipose tissues, pancreas, kidney, intestine, liver, and other internal organs was also increased in a cold environment, and accounted for 65% of the increase in blood flow during exposure to cold compared with only 36% in warm-acclimated rats. It is estimated that the extramuscular thermogenesis can account for a greater proportion of the total nonshivering thermogenesis in cold-acclimated rats. The contribution of brown adipose tissue is estimated not to exceed about 6% of the total heat production increase in cold-acclimated rats during exposure to cold.
Glycolytic rate in noradrenaline-treated albino rats exposed to low pressure
Authors: Kaur Surinder , Ghose A.
Published: April 2011

Daily exposure for 15 days to a pressure of 24 000 ft altitude caused a decrease of muscle and liver glycolytic rates in albino rats. On continuation of such exposures for [Formula: see text] months values returned to normal. When the same exposures were combined with a daily injection of noradrenaline, the decrease in glycolysis was prevented. In the latter case liver glycolysis did not show a change after treatment for 15 days or [Formula: see text] months; muscle glycolysis showed a marked increase after 15 days' treatment, and a moderate increase after [Formula: see text] months of treatment. Glycolytic data have been discussed in the light of hypoxic adaptation.
The Effects of Hydrostatic Pressure on the Elastic Properties of Cat Veins
Authors: Booking J. Kenneth , Roach Margot R.
Published: April 2011

Simultaneous measurements of pressure and volume were made on seven isolated external jugular veins and four femoral veins from cats. The measurements were made before and after the veins were held at an intraluminal pressure of 800 mm H2O. Circumferential tensions were calculated from Laplace's law (tension = pressure × radius). After being held at 800 mm H2O for periods of time up to 18 h, the resting radius of the vein increased and it became less distensible. Possible implications of these results concerning varicose veins are discussed. Since tension = pressure × radius, then as the radius increases and the pressure stays constant (as in varicose veins), the tension increases. If tension causes varicose veins then a vicious circle is set up which may result in the development of very severe varices.
Effects of Ethacrynic Acid on Frog Gastric Mucosa in Chloride Solutions
Authors: Dinno Mumtaz A. , Schwartz Manuel , Olson Axel K. , Carrasquer Gaspar
Published: April 2011

The addition of ethacrynic acid to a concentration of 1 mM in the nutrient solution bathing the frog gastric mucosa in vitro produced an immediate decrease in resistance followed by an increase in resistance and a decrease in H+ secretory rate. The latter effect was irreversible and the former reversible. During the initial phase for nutrient solutions of 4 mM K+ and 79 mM K+ containing 1 mM ethacrynic acid, the decrease in resistance was about 30% and the decrease in the transmembrane potential difference (P.D.) was about 1 mV in the low K+ case and 2 mV in the high K+ case. The addition of ethacrynic acid to a 4 mM K+ nutrient solution containing 1 mM Ba2+ produced initially a 19% decrease in resistance and both positive and negative changes in P.D. In the absence of Ba2+, these results suggest strongly a marked increase of K+ permeability with the possibility of some increase of Cl− permeability. In the presence of Ba2+, as a result due to the increased K+ resistance of the nutrient membrane, ethacrynic acid may affect predominantly either K+ or Cl− permeability.
Early Dissociation of Protein Synthesis and Amylase Secretion Following Hormonal Stimulation of the Pancreas
Authors: Mongeau R. , Couture Y. , Dunnigan J. , Morisset J.
Published: April 2011

The secretion of the various pancreatic enzymes can be increased by hormonal and cholinergic stimulation. However, it is not yet clear among the different investigators if their synthesis remains constant or can be modified according to different metabolic conditions. The secretion and synthesis of the pancreatic proteins were then studied in parallel to evaluate if secretion triggers synthesis or both phenomenons are controlled by separate mechanisms.The approach for these studies consists mainly in a combination of in vivo and in vitro experiments. The stimulants were injected in vivo and the pancreatic secretions were collected for different periods of time. The animals were then sacrificed and protein synthesis was measured in vitro along with the amylase secreted into the incubation medium. The results show that protein synthesis is decreased during the first 15 min after a single injection or infusion of both cholecystokinin–pancreozymin (CCK–PZ) and secretin. This reduction was associated with an increase in amylase secreted into the incubation medium. However, at 30 min after the hormonal stimulation, protein synthesis is increased while secretion into the incubation medium had returned to control levels. This increase in protein synthesis lasts for at least 1 h. These results strongly suggest that pancreatic enzyme secretion and synthesis are dissociated in the early minutes following hormonal stimulation.
The Blockade of Angiotensin Action by 8-Leu-Angiotensin on the Guinea-Pig Aortic Strip
Authors: LeMorvan P. , Palaic Dj. , Park W. K.
Published: April 2011

The action of angiotensin on the isolated guinea-pig aortic strip is shown in relation to other agonists. The apparent dissociation constant for angiotensin, as calculated from the dose–response curve, is 6.3 × 10−8 M. The blocking action of 8-Leu-angiotensin II on this preparation is specific for angiotensin since responses to other agonists are not modified. Complete reversibility of the blockade is demonstrated. A parallel shift to the right of the dose–response curve and attainment of maximum response indicate that the antagonism is competitive for angiotensin. It is concluded that 8-Leu-angiotensin II is a highly potent antagonist for angiotensin in this tissue.
Comparison of Dihydrotachysterol and 5,6-trans Vitamin D3 on Intestinal Calcium Absorption in Patients with Chronic Renal Failure
Authors: Gagnon R. , Ogden G. W. , Just G. , Kaye M.
Published: April 2011

The effect of dihydrotachysterol2 and of 5,6-trans vitamin D3 on calcium absorption in patients with severe chronic renal failure were compared. Dihydrotachysterol appeared to be more effective than the vitamin D analogue.
Uptake, Storage, and Release of γ-Aminobutyric Acid in Normal and Chronically Denervated Cat Cerebral Cortex
Authors: Reiffenstein R. J. , Neal M. J.
Published: April 2011

The uptake and release of γ-[3H]aminobutyric acid ([3H]-GABA) from chronically denervated, epileptic cerebral cortex of the cat has been compared with normal cortex. Both uptake and KCl-stimulated release of GABA appeared to be normal, although under the conditions of the experiment the resting release of GABA was elevated. Endogenous taurine and serine levels were increased, aspartate and glutamate decreased, while a variety of other amino acids, including GABA, were unchanged.
The Influence of Testosterone on the Endogenous Levels of Prostaglandin F in the Accessory Reproductive Glands of the Adult Male Rat
Authors: Sutherland D. J. B. , Telli A. H. , Singhal R. L.
Published: April 2011

Orchidectomy increased the endogenous concentration of prostaglandin F (PGF) in the prostatic and vesicular glands of adult rats. A single intramuscular dose of free testosterone (5.0 mg/100 g) was able to reverse the effects of castration on PGF concentration of the accessory reproductive organs. In the case of seminal vesicles, administration of testosterone to castrate rats markedly reduced the PGF levels within 144 h of hormone treatment.
The Effect of Noradrenaline and Tyramine on Cardiac Contractility, Cyclic AMP, and Phosphorylase a in Normal and Hyperthyroid Rats
Authors: Young Beverley A. , McNeill John H.
Published: April 2011

Noradrenaline and tyramine increased contractility, phosphorylase a, and cyclic AMP in a dose-dependent manner in the isolated perfused rat heart. Time–response studies revealed that cyclic AMP was increased by both amines before the increase in contractility. Hearts from hyperthyroid rats responded to noradrenaline in a manner similar to control hearts when contractility or cyclic AMP was measured. The phosphorylase activating effect of noradrenaline was enhanced in the hyperthyroid hearts. It was concluded that a non-cyclic AMP mechanism was involved in the enhancement. The effects of tyramine on contractility and cyclic AMP were decreased in the hearts from hyperthyroid animals when compared with control hearts. Phosphorylase activation by tyramine was not enhanced by the hyperthyroid state and was in fact reduced at higher doses of tyramine.
The Enhancement of Maximal Bilirubin Excretion with Taurocholate–Induced Increments in Bile Flow
Authors: Goresky Carl A. , Haddad Henry H. , Kluger Warren S. , Nadeau Brita E. , Bach Glen G.
Published: April 2011

Of the processes involved in the handling of a bilirubin load, the biliary secretory maximum or Tm for bilirubin has been regarded as rate limiting, and as a characteristic of liver function. In the present study, bile flow was varied by use of bile acid infusions, in order to determine whether the Tm is indeed constant or whether it varies with flow. Anesthetized dogs, with bile flow stabilized by cholinergic blockade, were studied during taurocholate infusions. In these animals the ductular component of flow is relatively inhibited and the bile flow rate increases approximately in proportion to the rate of excretion of taurocholate. The maximal biliary excretion rate of bilirubin was found to increase linearly with flow and taurocholate excretion, in a significant fashion, but, in contrast to the relation between taurocholate excretion and flow, a significantly large intercept remained on linear extrapolation towards zero flow. The basis for the large intercept is a great increase in the bilirubin concentration in bile as the flow is decreased. This results in a simultaneous sharp increase in the molar ratio (bilirubin/taurocholate) at very low flow rates.We have inferred, on the basis of the preceding data, that the capacity for bilirubin transport is linked to the secretion of bile acids into bile. At low rates of supply of bile acids, little of the material will reach the centers of the hepatic lobules, and the contribution of bile acids to bile flow at that site will be relatively low. At higher rates of bile acid infusion or supply, increased amounts of the bile acids will reach the centers of the lobules and contribute to increased bile formation in these areas. It appears that this is the mechanism which underlies the change in the transport maximum for bilirubin with change in the rate of bile salt excretion.
Noradrenaline Uptake Properties of the Anococcygeus Muscle of the Rat
Authors: Nash C. W. , Gillespie J. S. , Robertson E. N.
Published: April 2011

Noradrenaline (NA) uptake was measured in the anococcygeus by two methods: quantitative fluorescence microscopy and radioactive tracer techniques. A pharmacological analysis of the contribution of adrenergic nerve, smooth muscle, and nonspecific binding to collagen and basement membrane was attempted by studying the effects of desmethylimipramine and phenoxybenzamine on uptake. The importance of metabolic degradation in the process of NA accumulation was estimated by examining the effect of the combined use of iproniazid to inhibit monoamine oxidase and of β-thujaplicin to inhibit catechol O-methyltransferase.The results suggest that NA accumulation in this tissue at concentrations below 2 × 10−6 g/ml was almost entirely due to uptake into adrenergic nerves and to nonspecific binding. At higher concentrations of NA, above 2 × 10−6 g/ml, uptake into the smooth muscle cells began to contribute increasingly to the total accumulation. Inhibition of the metabolic enzymes increased the fluorescence of smooth muscle incubated with high concentrations of NA, confirming that only at those high concentrations was there any intracellular accumulation of NA and suggesting that the NA taken up by these smooth muscle cells is normally almost completely metabolized. Incubation with the inhibitors of catecholamine metabolism, and also with phenoxybenzamine, reduced both the fluorescence in the adrenergic nerve terminals and the accumulation of tritiated compounds by the whole tissue. Possible explanations for this observation are discussed.In the radioactive experiments 14C-sorbitol was used to measure the extracellular space (ECS). The ECS appeared to be a two-compartment system, a large, fast-filling and a small, slow-filling compartment. Electron micrographs suggest a possible basis for these two compartments in the large spaces between muscle bundles and the very narrow clefts between the cells in individual bundles. Quantitative estimates of the magnitude of these two spaces from electron micrographs are not incompatible with this.
Escape of Intestinal Resistance Vessels to Angiotensin II
Authors: McNeill J. Robert
Published: April 2011

The escape phase of the intestinal resistance vessel response to infusions of angiotensin II was studied in pentobarbital-anesthetized cats using a technique which did not involve cannulation of the arterial supply to the intestine. During intravenous infusions of angiotensin, the escape was 30% of the peak response. The escape was not related to the increase in arterial pressure. In low doses, the escape during intra-arterial infusions was similar to that observed during intravenous administration. Graded increases in the infusion dose of angiotensin produced increasing vasoconstriction except at high doses. The results indicate that escape of the intestinal resistance vessels to angiotensin is only partial and that a significant vasoconstriction is maintained. The results are consistent with the postulated role of endogenous angiotensin in the mechanism of the intestinal vasoconstriction following hemorrhage.
Experimental Validation of Nonsteady Rate Measurements using a Tracer Infusion Method and Inulin as Tracer and Tracee
Authors: Norwich K. H. , Radziuk J. , Lau D. , Vranic M.
Published: April 2011

In 1959, Steele (Ann. N.Y. Acad. Sci. 82, 420–430) suggested a method for measuring the rates of appearance (Ra) and of disappearance (Rd) of a metabolite in an intact system under conditions when Ra and Rd were changing with time. Steele's method involved modelling the system by a one-compartment model whose effective volume was assumed. To overcome the problem of assuming an effective volume, a model consisting of two compartments rather than one has been postulated. While no distribution volume need now be assumed, a preliminary steady state experiment is required for identification of the coefficients governing exchange of material between the two compartments.In five conscious dogs 14C-hydroxymethyl inulin (tracer) was infused at a constant rate, while unlabelled inulin (tracee) was infused at varying predetermined rates and the plasma concentrations of both were measured. These were then fitted by a series of smoothly joined polynomials. When the calculated rates of appearance of unlabelled inulin were compared with the actual rates, equally good results were obtained with the one-compartment (using the best effective volume) and the two-compartment models. The calculated values of Rd and of the clearance of inulin were not validated experimentally, but their validity is likely since the equations for Rd and Ra are related, and the Ra component has been validated. The identity of unlabelled inulin and the 14C-hydroxymethyl inulin species was ascertained by gel filtration, and by the identity of their in vivo kinetics.
Enhanced Binding of Chlorpromazine to Cholesterol-Depleted Synaptosome Fractions
Authors: Seeman P. , Lee T.
Published: April 2011

Brain synaptosome fractions were treated by Murphy's method in order to deplete the membrane cholesterol. The binding of 35S-chlorpromazine to these treated membranes was measured. It was found that the membrane/buffer partition coefficient of the drug was threefold greater in the treated synaptosome-rich fractions compared with the untreated fractions. The results suggest that cholesterol may not be a part of the membrane hydrophobic binding site for tranquilizers.
The Impulse-Blocking Concentrations of Anesthetics, Alcohols, Anticonvulsants, Barbiturates, and Narcotics on Phrenic and Sciatic Nerves
Authors: Staiman A. , Seeman P.
Published: April 2011

(1) The nerve-blocking potencies of anesthetics, alcohols, tranquilizers, antidepressants, anticonvulsants, barbiturates, and narcotics were obtained on the rat phrenic nerve and the sciatic nerves of the frog and the rat. Skou's second method for equilibrium blockade was used, and complete dose–response curves were obtained on the height of the compound action potential.(2) Uncharged drugs (alcohols, urethane) and acidic drugs (barbiturates, diphenylhydantoin) caused half blockade of the phrenic nerve (11 μm diameter fibers) at concentrations about 25–35% of those causing half blockade of sciatic nerve (16 μm fibers).(3) Tertiary amines (procaine, spirosuccinimide enantiomers, chlorpromazine, haloperidol, trifluperidol, methadone, and naloxone) produced half blockade of the phrenic nerve at concentrations about 10% of those producing half blockade of the sciatic nerve. Frog and rat sciatic C50% block values (i.e. the drug concentration that reduced the compound action potential by 50%) were the same.(4) The phrenic C50% block value for tetrodotoxin was 7.1 times higher than that for the sciatic nerve.(5) The phrenic C50% blockvalues of the neutral and acidic drugs (together as a group) correlated inversely with the membrane/buffer partition coefficients of the drugs, in accordance with the classical Meyer–Overton rule of anesthesia. The phrenic C50% block values for the tertiary amines also correlated inversely with the membrane/buffer partition coefficients. Tetrodotoxin did not fit on these two correlations, and appeared to fall into a category of its own.(6) It was concluded that, whether comparing different nerves or the same nerve at different stages of growth, smaller myelinated fibers required lower nerve-blocking concentrations of drugs.
A New Prolonged-Acting Type of Chlorpromazine: Behavioral Effects and Prolonged Actions on Nerve Membranes
Authors: Seeman P. , Machleidt H. , Kähling J. , Sengupta S.
Published: April 2011

A chlorethyl derivative of chlorpromazine was prepared (2-chlor-10-(3-(beta-chlor-ethyl)-methylammopropyl)-phenothiazine HCl). This drug stabilized human erythrocytes (from hypotonic hemolysis) in the micromolar concentration range and had prolonged nerve-blocking potency. By using a 14C-labelled form of this drug, it was found to adhere persistently to both erythrocyte and brain synaptosome membranes. In animal behavior tests, the drug (P-B 845 Cl) was about one-fourth the potency of chlorpromazine. There is a possibility that the drug may have some long-term action since the animals recovered more slowly from the antiamphetamine actions of P-B 845 Cl than from the anti-amphetamine actions of chlorpromazine.
Effects of Some Metallic Cations on Cerebral Cortical Neurones and Their Interactions with Biogenic Amines
Authors: Phillis J. W. , Limacher J. J.
Published: April 2011

The depressant action of calcium and various amines on rat cerebral cortical neurones is abolished by various agents which are known to have calcium-antagonist properties, such as manganese, cobalt, and verapamil. These agents, like calcium itself, depress neuronal excitability. After prolonged application (60–90 s) this depressant effect subsides, and repeated application not only of the desensitizing agent, but also of related substances, becomes ineffective for a period lasting up to 30 min. It is suggested that the calcium antagonists may act by displacing calcium from the cell membrane. Calcium thus released depresses cell excitability but is no longer available for release by subsequent applications of amines or antagonists. Barium reversed the calcium-antagonist block of aminergic depression on some cells, and had an amine-antagonizing action of its own on others. Barium depressed the excitability of many cortical neurones, and was itself antagonized by verapamil. Lithium reduced the depressant effects of noradrenaline on some neurones.
Cardiovascular Reactivity in the Dog after Chemical Sympathectomy with 6-Hydroxy dopamine
Authors: Gauthier Pierre , Nadeau Réginald A. , Champlain Jacques De
Published: April 2011

The cardiovascular responses to intravenous injections of noradrenaline, isoproterenol, and phenylephrine were studied in unanesthetized and anesthetized dogs before and after chemical sympathectomy with 6-hydroxydopamine (6-OH-DA), 50 mg/kg. Three days after 6-OH-DA pretreatment, the blood pressure response to noradrenaline in unanesthetized dogs was increased significantly despite the presence of a marked reflex slowing of the heart. Chronotropic and pressor responses to noradrenaline were likewise increased in anesthetized and vagotomized dogs after 6-OH-DA pretreatment. Not only was the amplitude of the responses to noradrenaline increased after 6-OH-DA pretreatment but their duration was likewise prolonged. In contrast, the cardiovascular responses to isoproterenol and phenylephrine did not appear significantly changed in 6-OH-DA pretreated dogs. These results are consistent with the development of a presynaptic type of supersensitivity in dogs pretreated with 6-OH-DA.
Differential Effect of Metabolic Inhibitors on Contractile Responses of Venous Smooth Muscle to Vasoactive Stimuli
Authors: Greenberg S. , Heitz D. C. , Long J. P.
Published: April 2011

The effect of metabolic inhibitors on norepinephrine (NE), epinephrine (E), tyramine (T), serotonin (5-HT), potassium chloride (KCl), and barium chloride (BaCl2) induced contraction was evaluated with the superfused canine dorsal metatarsal veins. ATP content was evaluated in the absence and presence of dinitrophenol, cyanide, azide, fluoroacetate, and iodoacetate. Contractile responses to vasoactive stimuli were measured before and during continuous superfusion with these inhibitors. Each of the metabolic inhibitors decreased tone and ATP. Dinitrophenol reduced the contractile responses of tibial arteries to NE, E, 5-HT, and KCl but abolished the contractile response to T and BaCl2. Cyanide and fluoroacetic acid did not significantly alter the contractile responses of tibial arteries to KCl or E but reduced the contractile responses to T, 5-HT, NE, and BaCl2. Azide reduced the responses to KCl, 5-HT, and T but not to NE, E, or BaCl2. Fluoroacetic acid reduced the responses to tyramine and serotonin but not to NE, E, KCl, or BaCl2. These findings are consistent with the conclusions that (1) vasoactive stimuli utilized different metabolic pathways to sustain their contractile response, (2) the adrenergic neuronal uptake mechanism or release process for catecholamines is more sensitive to metabolic inhibition than the contractile process, and (3) myogenic tone is more dependent on a functional oxidative metabolic pathway than the contractile responses to vasoactive stimuli.
Some Properties of Noradrenaline Uptake in Non-innervated Vascular Smooth Muscle
Authors: Triggle C. R. , Reiffenstein R. J.
Published: April 2011

The human umbilical artery, which does not receive adrenergic innervation, has been shown to bind small quantities of noradrenaline present in the perfusate. This binding is revealed both by the trihydroxyindole assay and by fluorescence histochemistry, and had one component which was only very slowly removed by prolonged washing. This may represent an intracellular uptake of noradrenaline. The trihydroxyindole technique was used to show that the uptake of noradrenaline by the umbilical artery is reduced by prior treatment with ouabain, phenoxybenzamine, cocaine, normetanephrine, or by lowering the temperature of the perfusate. This reduction in noradrenaline uptake is small, however, and cannot be detected by changes in fluorescence. These results are in contrast to those results obtained with innervated tissues, where pretreatment with those agents caused a very marked inhibition of noradrenaline uptake. This observation suggests that the mechanism of noradrenaline uptake by umbilical artery may be different from that in innervated tissues.
Comparative Effects of Prostaglandins A2 and B2 on Vascular and Airway Resistances and Adrenergic Neurotransmission
Authors: Greenberg Stanley , Howard Linda , Wilson William R.
Published: April 2011

Prostaglandin B2 (PGB2) may be formed from PGA2in vivo. The following study compares the effects of equivalent concentrations of PGA2 and PGB2 on systemic pressure, heart rate, airway resistance, cutaneous vascular resistance, and responses to sympathetic nerve stimulation and to norepinephrine and tyramine in the acutely denervated canine hind paw perfused with autologous blood at constant flow. Intra-arterial (i.a.) PGB2 (1 and 10 μg/min) produced concentration-dependent vasoconstriction. Fifteen minutes after PGB2 administration the pressor responses of the paw to sympathetic nerve stimulation were enhanced, whereas the pressor responses to norepinephrine and tyramine were unchanged. In contrast, low concentrations of PGA2 produced systemic and transient cutaneous dilation whereas the higher concentration (10 μg/min i.a.) produced systemic dilation and constriction of the acutely denervated paw. The pressor responses of the perfused paw to sympathetic nerve stimulation were enhanced with the higher infusion rate of PGA2. However, the pressor responses to norepinephrine and tyramine were unchanged during PGA2. In addition, PGB2, but not PGA2, increased airway resistance. These results suggest that: (1) PGB2 and PGA2 have different effects on systemic pressure and airway resistance but have similar effects on the cutaneous vascular bed; (2) both PGB2 and PGA2 selectively enhance neurotransmitter release from the catecholamine pool susceptible to activation by the nerve action potential; and (3) PGB2 is more potent in its ability to enhance neurotransmitter release than PGA2. The vasoconstriction and facilitation of sympathetic neurotransmission by PGA2 may be related to formation of PGB2 within the paw.
Hemodynamic Effects of CCl4 in the Intact Liver of the Cat
Authors: Lautt W. W. , Plaa G. L.
Published: April 2011

Blood flow in the intact liver of anesthetized cats did not change significantly over a period of 4 h following intraduodenal injection of CCl4 (1 ml/kg). Hepatocellular disruption was well underway by 2 h after the injection. Twenty-four hours following an oral dose of CCl4, the hepatic arterial resistance to blood flow was reduced and total blood flow to the liver was at least as high as in control animals. At this time, the hepatic artery appeared fully dilated and was less responsive to humoral (intra-arterial infusion of noradrenaline) and neural (reflex activation of the sympathetic nerves) constrictor influences. Thus, alterations in hepatic blood flow do not occur during the early phases of CCl4-induced hepatic injury. These data indicate that diminished blood flow is not a causative factor in the initial phases of CCl4-induced liver injury. By 24 h, hepatic blood flow is altered in such a manner that the damaged liver receives a higher proportion of arterial blood and a total blood flow that is not reduced in spite of a generally depressed cardiovascular system.
Acidic Aqueous Extraction of Hypothalamic Luteinizing Hormone Releasing Hormone to Study Biological Effects
Authors: Shin S. H. , Howitt C. J.
Published: April 2011

Several aqueous solvent systems were tested for their efficiency in extracting luteinizing hormone releasing hormone (LH-RH) from rat hypothalamus. Although LH-RH is a water-soluble decapeptide, neutral distilled water extracted only 10% of the LH-RH obtained using acid extraction methods. The efficiency of the acid extraction procedure suggests that in the hypothalamus the releasing hormone is bound to a relatively large molecular weight compound. Using the acidic extraction procedure, we found that hypothalamic LH-RH content is significantly lower in the castrated animal than in the normal rat.
On the Role of Neuronal Uptake (Uptake1) in the Inactivation of Noradrenaline by Aortic Strips
Authors: Wyse D. George
Published: April 2011

Inactivation of exogenous and neural noradrenaline was investigated in isolated rabbit aortic strips by a combination of the techniques of transmural stimulation and oil immersion. The latter technique was found to be a simple and reliable method for estimation of inhibition of the various intrinsic tissue pathways for inactivation of noradrenaline. Half-relaxation times ([Formula: see text]'s) of exogenous-noradrenaline responses were significantly increased by tropolone and cocaine. Cocaine had a slightly greater effect, increasing [Formula: see text] to 1.7–2.0 times the control value; tropolone increased [Formula: see text] to 1.2–1.3 times the control value. Iproniazid, tropolone and cocaine all significantly increased the [Formula: see text]'s of neural-noradrenaline responses. The enzyme inhibitors caused increases of 1.3–1.9, and cocaine, increases of 9–15 times the [Formula: see text]'s of neural-noradrenaline responses. Cocaine had a variable small effect on [Formula: see text]'s of responses to exogenous noradrenaline in aortic strips denervated by cold storage, and it is inferred that the post-junctional effect of cocaine contributes little to its effect on [Formula: see text]'s of fresh tissue. In conclusion, it is estimated that neuronal uptake can account for the disposition of approximately 50% of exogenous noradrenaline and 90% of neural noradrenaline in rabbit aortic strips. Studies with the oil-immersion technique and exogenous noradrenaline have probably underemphasized the importance of neuronal uptake in vascular tissue.
The Effect of Lanthanum on Excitation–Contraction Coupling in Frog Skeletal Muscle
Authors: Parry D. J. , Kover A. , Frank G. B.
Published: April 2011

Exposure of frog toe muscles to 1 mM La3+ results in a decrease in amplitude and rate of tension development of potassium contractures and twitches. At this concentration La3+ also inhibits the uptake of calcium, both in the resting condition and during stimulation. Caffeine contractures are unaffected even after a 5-min pre-exposure to La3+. The depolarization induced by various concentrations of K+ is reduced by about 10 mV as is the amplitude of the action potential. The rate of rise of the action potential is reduced by about 40% after 1 min in La3+ Ringer. Neither the decreased amplitude nor the reduced rate of depolarization is considered to be sufficient to explain the inhibition of tension development. It is suggested that La3+ partially uncouples excitation from contraction by preventing the release of a trigger-Ca2+ fraction from some site on the muscle membrane. This fraction normally plays a role in excitation–contraction coupling, although some tension may still be developed in the absence of a trigger-Ca2+ influx.
Localization in the Cerebellar Hemisphere of Climbing-Fiber Responses Evoked from the Trigeminal Nerve in the Cat
Authors: Miles T. S. , Cooke J. D. , Wiesendanger M.
Published: April 2011

The area of cerebellar cortex to which climbing fibers (CF) project from trigeminal cutaneous afferents has been established in pentobarbital-anesthetized cats. This area is centered upon the ipsilateral lobule HVI, with some overlap onto adjoining folia of the anterior lobe (lobule V) and onto crus Ia of lobule HVIIA. At almost all points within the projection area, CF field potentials of various amplitudes could be elicited by stimulation of more than one trigeminal branch. Hence the general somatotopic arrangement was a complex pattern of inputs converging onto many points from spatially related areas of facial skin. Convergence from more than one nerve was also seen on 32 of 47 single Purkinje cells.
Histrionicotoxin: Effects on Some Central and Peripheral Excitable Cells
Authors: Glavinović M. , Henry J. L. , Kato G. , Krnjević K. , Puil E.
Published: April 2011

Studies on the rat diaphragm confirmed previous reports that histrionicotoxin (HTX) reversibly blocks contractions, miniature end-plate potentials and depolarizations by ACh. Microiontophoretic applications of HTX in anaesthetized cats reversibly blocked spontaneous and glutamate-evoked discharges of spinal and cortical neurones, and strongly depressed responses of Renshaw cells to ACh or ventral root stimulation. HTX blocked the excitation of cholinoceptive cortical neurones by ACh or glutamate, and concomitantly reduced spike amplitudes. The similarity between effects of HTX and procaine may indicate a common mechanism of action.
Effects of Short Term Ether and Pentobarbital Anesthesia on Bone and Cartilage Metabolism
Authors: Simmons D. J. , Lesker P. A.
Published: April 2011

The effects of stress due to brief (4–5 min) ether and pentobarbital anesthesia vs. decapitation on assays of seven enzymes in homogenates of synovium, articular and epiphyseal cartilage, and metaphyseal and cortical bone were compared. Etherization caused twofold changes in synovial and articular cartilage G-6-PDH, LDH, CPK, glutamic DH, and ICDH based on tissue dry weight and DNA content. Pentobarbital anesthesia produced only slightly lower activities, per gram DNA, of LDH, acid phosphatase, and glutamic-DH in cortical bone. Epiphyseal cartilage metabolism was unaffected by either mode of anesthesia. No differences could be detected between the levels of enzyme activities of the several tissues taken from rats that had been decapitated or anesthetized with pentobarbital. The changes in enzyme activities suggested that pentobarbital was non-stressful and appropriate to metabolic studies in the skeleton.
The Effect of Cocaine, Reserpine, and 6-Hydroxydopamine on the Response of the Perfused Central Artery of the Rabbit Ear to Sympathomimetic amines
Authors: Yong Man Sen , Chen Pi-Chuan
Published: April 2011

The perfused central artery of the rabbit ear was less sensitive to extraluminal than to intraluminal noradrenaline, but the reverse was true for metaraminol, methoxamine, metanephrine, and isoproterenol. No difference was noted between the extraluminal and intraluminal potency of phenylephrine. Cocaine potentiated the effect of extraluminal and intraluminal noradrenaline, but decreased that of intraluminal phenylephrine. Irrespective of the route of administration, the constrictor potencies of other sympathomimetic amines were not affected by cocaine. Arteries of reserpine-treated rabbits were supersensitive to extraluminally and intraluminally applied noradrenaline and phenylephrine, but they were not supersensitive to metaraminol. 6-Hydroxydopamine effectively destroyed adrenergic nerve endings of the central ear artery and increased its responses to both extraluminal and intraluminal noradrenaline and phenylephrine. However, only the constrictor potencies of intraluminally applied metaraminol and methoxamine were enhanced by 6-hydroxydopamine. The apparent discrepancies between the results obtained by various procedures that eliminate or impair the nerve uptake process suggest that the difference in the constrictor potency of extraluminal and intraluminal sympathomimetic amines is probably unrelated to their uptake by nerves located in the adventitio–medial junction of the artery.
Molecular Structure–Activity Relationships of Hydrazides Inhibiting Glutamic Acid Decarboxylase, GABA-α-Oxoglutarate Aminotransferase, and Monoamine Oxidase Activities in Chick Brain
Authors: Wood J. D. , Gorecki D. K. , Dimmock J. R. , Hawes E. M.
Published: April 2011

Several aryl and heteroaryl hydrazides were synthesized and evaluated for their inhibitory effects on glutamic acid decarboxylase (GAD), GABA-α-oxoglutarate aminotransferase (GABA-T), and monoamine oxidase (MAO) enzyme systems in chick brain 24 h after their intramuscular administration (0.75 mmol/kg). All compounds produced a reduction in GAD, GABA-T, and MAO activity. Structure–activity relationships indicated that the ring structure had a greater influence on the degree of GAD and GABA-T inhibition than did the N′-terminal group. In contrast, structural requirements for MAO inhibition were much more restrictive. The intramuscular administration of benzoic acid hydrazide to chicks 24 h prior to their being exposed to oxygen at high pressure provided significant protection against the onset of the hyperbaric oxygen-induced seizures.
The Influence of Prolonged Hyper-and Hypothyroid States on the Noradrenaline Content of Rat Tissues and on the Accumulation and Efflux Rates of Tritiated Noradrenaline
Authors: Tu T. , Nash C. W.
Published: April 2011

The influence of chronic hyper- and hypothyroidism on the uptake and retention of tritiated noradrenaline ([3H]NA) and on the endogenous noradrenaline (NA) content of various adrenergically innervated tissues was studied in thyroidectomized and sham-operated euthyroid rats. Half of the thyroidectomized rats were treated daily with thyroxine (25 μg/kg) for 3 or 12 weeks to simulate a condition of chronic hyperthyroidism, while the other half was left untreated to form a hypothyroid group. The body weight and the heart rate of each rat were measured at the end of each experiment, and in addition, at the end of the 3 week experiment, the oxygen consumption and the plasma thyroxine levels were measured to confirm the thyroid state of the animals. At the end of both experiments, each animal was given an intravenous injection of [3H]NA and the [3H]NA and the total endogenous NA content of the heart and various other adrenergically innervated tissues were measured on a timed schedule, to compare the initial accumulations and the rates of efflux of [3H]NA under different thyroid states. Although the hyperthyroid rats had higher heart rates and heart weights, they were not significantly different from the euthyroid controls with respect to their body weights, tissue NA content, or accumulation and efflux rates of [3H]NA. In contrast, the hypothyroid rats showed significantly lower heart rates, body weights, and heart and other tissue weights, but higher tissue concentrations of NA and rates of efflux of [3H]NA than the euthyroid group. In the hypothyroid state, the NA turnover appeared to be increased as the [3H]NA efflux rate was increased from the hearts and adrenal glands. There were no significant differences between the results of the 3 week and the 12 week experiments and no evidence that prolongation of the hyperthyroid state gave different results from those found by other workers who used much shorter treatment periods and larger doses of thyroxine to develop hyperthyroidism.
Multiple Hepatic Excretory Mechanisms for Organic Anions. A Study with Succinylsulfathiazole and Taurocholate in the Rat
Authors: Bailey D. G. , Johnson G. E.
Published: April 2011

A study was done to investigate interactions in the biliary excretion of [14C] succinylsulfathiazole and [3H]taurocholate after intravenous administration of the two compounds to anesthetized rats. Either compound administered alone increased bile flow and was excreted in the bile. The simultaneous infusion of both significantly increased bile flow above the values seen when either was given alone. However, the biliary-excretion rates of both compounds and their concentrations in bile were reduced when they were administered concomitantly. The simultaneous injection of radioactive taurocholate and succinylsulfathiazole did not alter significantly the plasma concentrations of either compound or their binding to plasma proteins from the values obtained when each was given alone. These results are consistent with a concept of competition between these compounds for the same liver-to-bile transport system. They contrast with previous observations that indicated that the concomitant administration of taurocholate increased the biliary excretion of acidic compounds. In the light of this work, it might be suggested that there are more than one transport system for the biliary excretion of organic anions.
Comparative Pharmacological Studies on Butriptyline and Some Related Standard Tricyclic Antidepressants
Authors: Jaramillo J. , Greenberg R.
Published: April 2011

Butriptyline was compared with imipramine and other tricyclic antidepressants for its ability to modify: (a) contractions of the cat nictitating membrane induced by noradrenaline (NA) and 5-hydroxytryptamine (5-HT), (b) the adrenergic neuron blocking action of guanethidine in the guinea pig vas deferens, (c) the rabbit's electroencephalogram (EEG) and physostigmine arousal, and (d) the sleep pattern of the rat. Imipramine and amitriptyline potentiated the NA and 5-HT effects on the nictitating membrane and antagonized the inhibitory actions of guanethidine in the guinea pig vas deferens, whereas iprindole and butriptyline were ineffective. These results are consistent with the ability of these drugs to block the neuronal uptake of catecholamines. Butriptyline was a potent blocker of the arousal reaction induced by physostigmine. Butriptyline (20–30 mg/kg) and amitriptyline (10–20 mg/kg) reduced rapid eye movement sleep with a concomitant increase in non-rapid eye movement sleep. This may be a reflection of the dual activity observed in the clinic with these compounds, namely, antidepressant and antianxiety effects.
Effects of Adrenaline on the Dynamics of Carbohydrate Metabolism in Rats Treated Chronically with Adrenaline
Authors: Rousseau-Migneron Suzanne , LeBlanc Jacques , Lafrance Louise , Depocas Florent
Published: April 2011

Following a subcutaneous injection of adrenaline (300 μg/kg), blood-glucose levels were lower in rats treated chronically with adrenaline (300 μg/kg twice a day for 28 days) than in control rats during at least 2.5 h after the injection. To explain this difference of response, the turnover rate of glucose was measured in control and adrenaline-treated rats during adrenaline infusion (0.75 μg/kg−1 min−1), with [U-14C]glucose as tracer. It was found that the rate of appearance of glucose was greater in the control than in the adrenaline-treated group after a 120-min infusion of adrenaline. The rate of disappearance of glucose in the treated rats increased during the first 60 min of infusion and stayed at this elevated level for a subsequent 2 h, whereas in the control rats, it remained unchanged at the beginning of adrenaline infusion and significantly increased only during the second and third hours of infusion. In addition, the metabolic-clearance rate of glucose was not modified by adrenaline in the treated group, but in the control group, the initial clearance rate was significantly less than in the treated group, and decreased during the first hour of adrenaline infusion even though blood glucose reached values of 244 mg/100 ml. From these data, it is suggested that rats adapt to a chronic exogenous supply of adrenaline by a reduced increase in glucose production in response to adrenaline infusion and a better glucose utilization, which possibly indicates a decrease in the inhibitory effect of adrenaline on insulin secretion.
Intestinal Calcium-Binding Protein in Animals Fed Normal and Rachitogenic Diets: I. Rat Studies
Authors: Harrison Joan E. , Hitchman A. J. W. , Tam C. S.
Published: April 2011

Measurements were made of duodenal calcium-binding protein (CaBP) on rats during development of rickets and, subsequently, following vitamin-D2 treatment.Results showed a poor inverse correlation between duodenal CaBP and rickets. In rats fed a phosphate-deficient rachitogenic diet, duodenal CaBP concentration finally fell below detectable limits, but CaBP was still readily measurable 2 weeks after rickets was clearly established. Following a massive dose of vitamin D2 (50000 I.U.) to rachitic animals, CaBP was formed. However, a small dose of vitamin D2 (500 I.U. daily for 4 days) was insufficient to demonstrate CaBP synthesis even though it was sufficient to demonstrate calcification of cartilage. Administration of normal rat chow to rachitic rats stimulated greater CaBP synthesis than vitamin-D treatment alone. The rachitogenic diet supplemented with phosphate, which caused osteoporosis but not rickets, inhibited CaBP synthesis. The results suggest that nutritional deficiencies from the rachitogenic diet, in addition to vitamin-D deficiency, inhibited CaBP synthesis.
Substance P and Spinal Neurones
Authors: Henry J. L. , Krnjević K. , Morris M. E.
Published: April 2011

When applied by microiontophoresis, substance P (sP) had a strong, but slow and prolonged excitatory action on nearly half the neurones tested in the lumbar spinal cord of cats. Motoneuronal antidromic field potentials only occasionally showed a significant effect of sP. Cerebral cortical neurones in cats and rats were much less readily excited than spinal interneurones. Some unresponsive units showed evidence of a depressant effect of sP. Although sP may have a significant function in central afferent pathways, it is not likely to be a quickly-acting synaptic transmitter.
Phosphorylation of the Membrane Components of Chromaffin Granules: Synthesis of Diphosphatidylinositol and Presence of Phosphatidylinositol Kinase in Granule Membranes
Authors: Trifaró J. M. , Dworkind J.
Published: April 2011

Adenosine triphosphate (ATP) induces the release of catecholamines, endogenous ATP, and soluble protein from chromaffin granules isolated from the adrenal medulla. When ATP exerts this action, it is hydrolyzed by enzymes present in the granule membrane, and part of the Pi liberated from ATP is transferred to the protein and lipid of the granule membrane. The phosphorylated lipid component, which was identified by thin-layer and ion-exchange chromatography as diphosphatidylinositol, was formed from ATP and monophosphatidylinositol. This latter phospholipid was the substrate for the enzyme phosphatidylinositol kinase. Both substrate and enzyme are components of the granule membranes, because they have a similar subcellular distribution as dopamine β-hydroxylase (a granule membrane marker). The formation of diphosphatidylinositol was Mg2+-dependent, it was further stimulated by Mn2+, it was inhibited by N-ethylmaleimide and the reaction had an optimal pH of 5. The synthesis of diphosphatidylinositol was also shown to occur in chromaffin granules "in situ" during the stimulation of the adrenal medulla by acetylcholine.