bluuebunny/crossref_metadata_2025 huggingface dataset:
The guinea pig tracheobronchial spiral strip: responses to selected agonists
Authors: Hanna C. J. , Roth S. H.
Published: April 2011

The guinea pig tracheal spiral strip is a useful preparation for studying bronchoconstrictor and bronchodilator compounds. Employing a simple and rapid modification of this technique, experiments were performed in vitro to quantitate the effects of selected bronchospastic agents on guinea pig tracheobronchial smooth muscle. Three sections of the main airways were prepared from each animal: an upper tracheal, a lower tracheal, and a bronchial segment. The dose-dependent contractile responses of the three tissue segments were determined for carbachol, acetylcholine, histamine, 5-hydroxytryptamine, and bradykinin, Differences were observed amongst the agonists in magnitudes of contraction, effective concentration ranges, and slopes of dose–response curves. ED25, ED50, and ED75, values were calculated from regression analysis of dose–response data. The relative order for these agents to produce maximum contractions was found to be carbachol [Formula: see text] acetylcholine > histamine > 5-hydroxytryptamine > bradykinin. Furthermore, it was found that there was no significant difference between the three tissue segments in their responses to the various agonists.
The luteolytic effect of prostaglandin F2α on the guinea pig corpus luteum in relation to gonadotropins and stages of the oestrons cycle
Authors: Tso E. C.-F. , Tam W. H.
Published: April 2011

When hysterectomized guinea pigs were treated daily with prostaglandin F2α, (0.058 mg PGF2α/100 g body weight per day), luteal volumes and systemic levels of progesterone were unaffected up to day 9 of the oestrous cycle, but the onset of luteolysis had occurred around day 12, 3–4 days earlier than normal. The treatment of hysterectomized animals on days 5–7 and 8–10 at the same dose did not result in luteal regression in any respect on day 14, but treatment on days 9–12 and days 9–13 induced luteolysis. A continuous treatment with 0.135 mg PGF2α/100 g body weight per day reduced the cycle length by 22%, but again luteal volume and progesterone level were unaffected up to day 9. The treatment with human chorionic gonadotropin (50 IU/day) or follicle-stimulating hormone (5 U/day) on days 8–13 had an antagonistic effect on the luteolytic action of PGF2α administered on days 9–13, but prolactin also administered at this time did not have this effect. It is postulated that, in guinea pigs, ovulation and the formation of corpus luteum (CL) are not affected by a low dose of PGF2α, the CL is protected from PGF2α by gonadotropins up to day 9, normal luteolysis is due to the withdrawal of gonadotropins and the upsurge of PGF2α, and the subsequent rate of luteal regression depends on the amount of available PGF2α.
Enzymatic degradation of somatostatin by rat plasma and hypothalamus
Authors: Dupont A. , Alvarado-Urbina G. , Côté J. , Labrie F.
Published: April 2011

A highly sensitive and specific radioimmunoassay for somatostatin has been used to study inactivation of the neurohormone by plasma and hypothalamic peptidase(s). Specificity of the inactivation process was indicated by the absence of interference by addition of luteinizing hormone releasing hormone, thyrotropin-releasing hormone, oxytocin, or substance P. The inactivating ability of hypothalamic tissue and plasma was destroyed by heating and the protease inhibitor benzamidine prevented plasma activity, thus suggesting the enzymatic nature of the processes involved. The present data suggest that the inactivation of somatostatin by hypothalamus and plasma could be an important factor in the regulation of circulating somatostatin levels.
The ganglionic blocking properties of the cholinesterase reactivator, HS-6
Authors: Lundy Paul M.
Published: April 2011

Following intravenous administration of the cholinesterase reactivator HS-6 (30 mg/kg), blood pressure fell (up to 50 mmHg) and maximal blood levels of HS-6 reached 242 μg/ml. HS-6 attenuated the pressor response resulting from carotid occlusion and the depressor effect of vagal stimulation. Doses of HS-6 below those used to protect against soman in different animal species (10–30 μmol/kg) progressively blocked the ganglion-stimulating effects of nicotine and dimethylphenylpiperazinium but not the pressor effect following adrenaline, a pattern similar to that produced by hexamethonium but only [Formula: see text] as potent. HS-6, like hexamethonium and mecamylamine, progressively blocked the contraction of the nictitating membrane of the cat resulting from preganglionic stimulation.The results indicate that HS-6 possesses ganglion-blocking properties at doses likely to be used in the protection against soman poisoning. The ganglion-blocking properties of the drug may be a factor in the beneficial effects of HS-6.
A presynaptic component of the action of iontophoretically applied flurazepam on feline cortical neurones
Authors: Nestoros J. N. , Nistri A.
Published: April 2011

The effect of iontophoretically applied flurazepam on the spike activity of pericruciate cortical neurones of the cat was studied. Flurazepam increased cortical inhibition produced either by local electrical stimulation (which is known to release γ-aminobutyric acid (GABA)) or by iontophoretically applied GABA. Following intravenous treatment with thiosemicarbazide (a GABA-synthesis inhibitor), flurazepam still augmented the action of GABA but was much less effective on electrically evoked cortical inhibition. These findings suggest that part of the action of flurazepam on inhibitory cortical transmission might be at the presynaptic level.
Epileptiform seizures in domestic fowl. IX. Implications of the absence of anticonvulsant activity of ethosuximide in a pharmacological model of epilepsy
Authors: Davis H. L. , Johnson D. D. , Crawford R. D.
Published: April 2011

Acute dose–response studies were conducted to determine if ethosuximide had anticonvulsant activity against seizures evoked by stroboscopic stimulation of epileptic fowl and to correlate the observed effects with the concentration of the drug in the plasma. Ethosuximide, in doses that produced mean plasma concentrations of 366 μg/ml and signs of sedation, did not reduce seizure susceptibility. Twice daily administration of ethosuximide produced mean plasma concentrations of 430 μg/ml after 36 h without affecting seizure susceptibility even in the presence of marked sedation. Previous studies have shown that epileptic fowl are sensitive to the anticonvulsant effects of phenobarbital, phenytoin, and primidone at plasma concentrations similar to those required in humans. Since ethosuximide has a high specificity against petit mal seizures in humans, the failure of ethosuximide to provide protection indicates that epileptic fowl represent a relatively specific pharmacological model for drugs effective against generalized tonic–clonic and focal cortical epilepsies in humans.
Ranking of excitatory amino acids by the antagonists glutamic acid diethylester and D-α-aminoadipic acid
Authors: Hicks T. P. , Hall J. G. , McLennan H.
Published: April 2011

A separation of the excitatory actions of the amino acids upon thalamic neurones of rats anaesthetized with urethane has been accomplished through the use of two antagonists. It has been possible to rank the excitatory compounds in their order of susceptibility to D-α-aminoadipic acid (DαAA) and L-glutamic acid diethylester (GDEE). The observation that the ranking orders of the excitants differ for these two antagonists permits an analysis of the types of receptors with which the amino acid excitants react. The results support the proposition that more than one neuronal receptor sensitive to the amino acids exists.
Photoaffinity labeling of the angiotensin II receptor; pharmacology of the labeling peptides in the dark
Authors: Escher E. , Nguyen T. M. D. , Regoli D.
Published: April 2011

The biological activities of photoaffinity labeling analogs of angiotensin II (ATII) and their precursors were measured in rabbit aorta strips in the dark. Most of the analogs behave as reversible, specific agonists, one as a competitive inhibitor. The activities are discussed in line with the current view of structural requirements. The modifications consisted of substitutions on the aromatic nuclei of Tyr4 and Phe8 in [Sar1]ATII with (4′-NO2)Phe, (4′-NH2)Phe, (4′-N3)Phe, (4′-N2+)Phe, and (4′-NH2-3′, 5′-I2)Phe. It is shown that the affinity of the ATII analogs modified in position 4 depends on the electronegativity and not on space-filling properties of the aromatic residue; rising electronegativity lowers the affinity, i.e., [Sar1, (4′-NO2)Phe4]ATII has no more measurable activity. Substituting the aromatic side chain in position 8 of [Sar1]ATII gives well-binding analogs with intrinsic activities from 0 to 100% and activity seems to depend only on stereochemical requirements. Agonists and partial agonists bear rather small groups like -NH2, -N3, -NO2, and -N2+. The only antagonist [Sar1, (4′-NH2-3′,5′-I2)Phe8]ATII resembles the antagonist [Sar1, Leu8]ATII in competitivity and binding.
The relationship of deep and surface skin temperatures to the ventilatory responses elicited during cold water immersion
Authors: Martin Sheilagh , Cooper K. E.
Published: April 2011

Subjects were immersed for 10 min in water at 14.5 °C, after exposure either to ambient temperature or sauna heating. During the immersions, total ventilation, end-tidal [Formula: see text], the mean of three surface skin temperatures, and deep skin temperatures were measured. There was a statistically significant correlation between the rate of change of deep skin temperature and the initial ventilatory responses evoked during both cold water immersions. After the sauna heating and cold water exposure, the temperature gradient through the skin appeared to be related to the ventilatory response. There was no significant correlation between the rate of change of mean surface skin temperature and the ventilatory response. The results suggest that the primary drive to increased ventilation during cold water immersion is the rate of change of deep skin temperature.
Effects of Cortisol on adrenal phenylethanolamine-N-methyltransferase: Antagonistic effects of vitamin D in hypophysectomized rats fed a vitamin D free diet
Authors: Brion F. , Parvez S. , Parvez H. , Marnay-Culat C. , Raoul Y.
Published: April 2011

The influence of individual or combined administration of vitamin D and hydrocortisone on adrenal phenyl-N-methyltransferase (PNMT) in hypophysectomized rats deprived of vitamin D for 1 month has been studied, as well as adrenal and urinary epinephrine and norepinephrine. Daily administration of vitamin D for 11 days decreased PNMT activity and increased adrenal norepinephrine, whereas adrenal epinephrine remained unaffected. Epinephrine and norepinephrine urinary excretion increased after four and nine injections of vitamin D from the hypophysectomized rats fed a vitamin D free diet for 1 month. Hydrocortisone treatment produced increases in adrenal PNMT and epinephrine as well as in urinary excretion of both monoamines. The effects of individual administration are neutralized when the two products are injected together.
Effects of SITS on choride permeation in Xenopus skeletal muscle
Authors: Vaughan Peter , Nok Fong Chin
Published: April 2011

Small signal cable analysis has been used to estimate the resting membrane chloride conductance of sartorius muscle fibres of Xenopus laevis. Muscles were bathed in solutions in which potassium was replaced by rubidium at pH's 8.8, 7.04, and 5.25. The conductance ratio in these solutions was 12:5:1. The conductance was significantly reduced at all pH's by the addition of 4-acetamido-4′-isothiocyano-2,2′-stilbene disulphonic acid (SITS). Rubidium conductance was determined as the membrane conductance in a solution in which potassium was replaced by rubidium and chloride was replaced by sulphate. Rubidium conductance was not pH sensitive. Subtraction of rubidium conductance indicated that 0.2 mM SITS reduced chloride conductance by about 50%, regardless of pH, and 1 mM SITS reduced it by at least 75%. When 2 mM SITS was added to solutions containing 120 and 30 mM chloride (2.5 mM potassium) the membrane potential of the muscle became insensitive to changes of chloride concentration in the bathing medium.It is concluded that SITS exerts a blocking effect on chloride conductance and permeability in Xenopus muscal membrane by binding to a site in the chloride channel that is not itself sensitive to the external pH.
Reticuloendothelial system blockade-induced humoral factor depletion and susceptibility to hemorrhagic shock
Authors: Loegering Daniel J. , Schneidkraut Marlowe J.
Published: April 2011

This study was carried out to determine if reticuloendothelial system (RES) Mockade-induced depletion of circulating alpha-2-glycoprotein opsonic activity resulted in increased susceptibility to hemorrhagic shock. RES blockade induced by the injection of gelatinized lipid emulsion was associated with a 45.9% decrease in phagocytic index and a 85.7% decrease in plasma alpha-2-glycoprotein opsonic activity. Animals subjected to RES blockade 30 min prior to hemorrhagic shock showed a decrease in time to decompensation and a decrease in maximum shed volume. These results are consistent with the concept that circulating levels of this opsonic protein are important in modulating RES phagocytic function and in host defense to shock.
Picrotoxin prevents habituation of the gill withdrawal reflex in Aplysia
Authors: Lukowiak Ken
Published: April 2011

The gill withdrawal reflex evoked by tactile stimulation of the siphon in Aplysia habituates with repeated presentation of the stimulus. This adaptive behaviour is mediated by the integrated activity of the central (CNS) and peripheral (PNS) nervous systems. The PNS mediates the basic reflex and its habituation while the CNS exerts both suppressive and facilitatory control over the PNS. This results in greater adaptability of the reflex behaviours. In young Aplysia the CNS control is absent and this is due to the incomplete development of pathways in the CNS. In an attempt to identify the pathway an attempt was made to manipulate the CNS's suppressive influence by agents which antagonize putative neurotransmitters. The application of picrotoxin-containing seawater over the CNS removed the CNS's suppressive influence but not its facilitatory influence. Thus the reflex amplitude was increased, the reflex latency decreased, and repeated stimulation did not result in habituation. This effect of picrotoxin was completely reversible. It is thus proposed that γ-aminobutyric acid, a putative neurotransmitter, plays an important rote in the mediation of the CNS's suppressive influence.
Inhibition of γ-aminobutyric acid uptake into astrocytes by pentobarbital
Authors: Hertz L. , Sastry B. R.
Published: April 2011

Pentobarbital (0.5–2 mM), but not phenobarbital, was found to inhibit the uptake of γ-aminobutyric acid into mouse astrocytes in primary cultures by up to 45%. This inhibition was additive to a reduction in uptake rate caused by excess potassium. Its possible role in the pharmacological action of pentobarbital is discussed.
Unusual particle trajectories and structural arrangements in myelinated nerve fibers
Authors: Smith Richard S. , McLeod Keith D.
Published: April 2011

Others have reported that axonally transported particles, which usually travel in a direction roughly parallel to the axis of the nerve fiber, may suddenly shift sideways as though changing tracks. Examples of this rare type of movement are shown for particles undergoing transport in myelinated axons of Xenopus laevis. An examination of the structure of axons from Xenopus showed that some microtubules, neurofilaments, and elements of endoplasmic reticulum may also exhibit marked deviations from the axial direction. It is concluded that it is not necessary to propose any mechanism for changing tracks in order to explain the particle motion.
Hypothalamic projections of renal afferent nerves in the cat
Authors: Ciriello J. , Calaresu F. R.
Published: April 2011

In 10 cats anaesthetized with chloralose the electrical activity of spontaneously active hypothalamic units was recorded for changes in discharge rate during electrical stimulation of renal afferent nerves. The discharge rate of 141 single units was altered by stimulation of either the ipsilateral or contralateral renal nerves. Most of the responsive units were located in the regions of lateral preoptic nucleus, lateral hypothalamus, and paraventricular nucleus. These results demonstrate that renal afferent nerves provide information to hypothalamic structures known to be involved in the regulation of arterial pressure and fluid balance.
Effect of p-chlorophenylalanine on the acquisition of tolerance to the hypnotic effects of pentobarbital, barbital, and ethanol
Authors: Khanna J. M. , Kalant H. , Lê A. D. , Mayer J. , LeBlanc A. E.
Published: April 2011

Rats were given pentobarbital by daily intubation. Sleeping times and blood levels of drug at awakening, after intraperitoneal test doses of ethanol, pentobarbital, or barbital, were measured at various times during chronic treatment in order to assess the degree of tolerance developed. No central nervous system (CNS) tolerance to pentobarbital or cross-tolerance to barbital or ethanol occurred on treatment with sodium pentobarbital, 50 mg/kg, daily. However, when the size and frequency of pentobarbital treatment doses were increased (50–80 mg/kg, three times daily) a clear CNS tolerance to barbital occurred. Chronic administration of p-chlorophenylalanine (p-CPA), in a dose previously shown to maintain more than 95% depletion of brain serotonin (5-HT), enhanced the acute hypnotic effect of barbiturates and ethanol. Independently of this effect, p-CPA treatment also resulted in a reduction in the development of CNS tolerance. These results are consistent with earlier findings that brain 5-HT depletion retards tolerance development to central depressant drugs as measured by a variety of unrelated tests.
Efflux du 36Cl et distribution du Cl dans le muscle papillaire du lapin, effet de l'ouabaïne
Authors: Caillé Jean-Pierre
Published: April 2011

The 36Cl efflux "in vivo" was measured in the rabbit papillary muscle to determine the Cl distribution in the muscle and to evaluate the effect of ouabain on this parameter. The results obtained for the 36Cl efflux are analyzed using either a two-compartment model or a model including diffusion in the extracellular space in series with one compartment. The Cl exchange with 36Cl, *[Cl]i (intracellular Cl content which has participated in exchanges. [Formula: see text]) is computed from the exponential terms of the models. A time exposure of 40 and 80 min to the 36Cl-containing solution led to the same exchange Cl content: 20.5 and 23.9 mmol/kg cells. Addition of ouabain (10−6M) slightly increased the rate constant of the cellular compartment, but did not influence the *[Cl]i. In the presence of ouabain (10−6M), there was a significant increase in the efflux component with a rapid rate constant. These results can be interpreted as follows: the Cl intracellular concentration is not affected by ouabain; thus, the increase in total Cl content induced in the papillary muscle by ouabain is located in a compartment having a very rapid exchange velocity with the extracellular medium.[Journal translation]
Implications of the finding of calcium carbonate in rabbit urine with respect to renal acidification
Authors: Tam S.-C. , Goldstein M. B. , Chen C. B. , Halperin M. L. , Stinebaugh B. J.
Published: April 2011

Formation of calcium carbonate or carbamino compounds in a bicarbonate solution should generate hydrogen ions and thereby elevate the [Formula: see text] of that solution. The presence of these substances in rabbit urine was established by demonstrating a significantly lower value for urine total carbon dioxide content measured by microgasometry (number of moles) than with the titration technique (number of equivalents).As there was a significant correlation between the calcium and the carbonate contents in the urine, we surmised that most of the carbonate was in the form of a suspension of calcium carbonate. Direct analysis of precipitates from rabbit bladders confirmed this impression.The formation of calcium carbonate in a solution should raise the [Formula: see text], by the reaction: [Formula: see text] with subsequent dehydration of the H2CO3. In vitro studies demonstrated that the addition of 1 mmol calcium to 1 L of a 200 mM bicarbonate solution raised the [Formula: see text] by approximately 50 mmHg (1 mmHg = 133.322 Pa). However, in vivo measurements of the [Formula: see text] of rabbit urine containing a similar quantity of calcium carbonate revealed that there was no such rise in vivo (urine values = blood values). Therefore, the formation of calcium carbonate should have occurred at an earlier site in the nephron, thereby allowing the [Formula: see text] to diffuse into peritubular capillaries during transit through the nephron.
Free fatty acids as a determinant of myocardial oxygen consumption: a caveat
Authors: Dagenais Gilles R. , Rouleau Jacques R. , Côté Isabelle
Published: April 2011

The present study was designed to determine whether the antilipolytic agent β-pyridylcarbinol modifies left ventricular blood flow distribution. It has been shown that the administration of this agent during isoproterenol infusion reduced both myocardial oxygen consumption and myocardial free fatty acid uptake. Although attributed to a decrease in myocardial free fatty acid uptake, the reduction in myocardial oxygen consumption might also be due to a modification in left ventricular blood flow distribution induced by β-pydidyiearbinol. To verify this possibility left ventricular blood flow distribution was measured with radioactive microspheres in 10 anesthetized dogs during control, during an infusion of isoproterenol (0.2 μg∙kg−1∙min−1) alone, and during an isoproterenol plus β-pyridylcarbinol infusion (0.1 mg∙kg−1∙min−1). In comparison with the control observations, isoproterenol infusion induced a significant increase of 37% in heart rate and of nearly 100% in myocardial free fatty acid uptake, myocardial oxygen consumption, and coronary blood flow, but did not affect the left ventricular blood flow distribution. The addition of β-pyridylcarbinol to the isoproterenol infusion did not cause any significant changes in left ventricular blood flow distribution, although it reduced myocardial free fatty acid uptake by 67% (p < 0.01). Despite this reduction, myocardial oxygen consumption did not change. However, in dogs with a myocardial oxygen uptake above 12.5 mL∙min−1∙100 g−1 during isoproterenol infusion, there was a reduction in myocardial oxygen consumption when β-pyridylcarbinol was added, without significant change in left ventricular blood flow distribution. The present findings reveal that β-pyridylcarbinol does not modify left ventricular blood flow distribution and that the determinant role of free fatty acids on myocardial oxygen consumption is restricted to conditions with increased myocardial demand.
Insulin and glucagon in rats with Islet cell tumors Induced by small doses of streptozofoclii
Authors: Yoshino Gen , Kazumi Tsutomu , Morita Soichiro , Baba Shighaki
Published: April 2011

Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma glucagon levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 ± 8.60 and 35.07 ± 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 ± 0.61 and 2.24 ± 0.67 μg/g wet weight, respectively).These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.
Variability and temperature dependence of the velocity of retrograde particle transport in myelinated axons
Authors: Smith Richard S. , Cooper Paul D.
Published: April 2011

The velocity of the retrograde transport of optically detectable particles was studied in isolated myelinated axons from Xenopus laevis at room temperature and with varying temperature. At room temperature (22–23.1 °C) the mean particle velocity was significantly different in some axons of the same animal. Results pooled from a number of axons did not indicate any significant difference in the average particle velocity in different animals. At room temperature, even though the mean particle velocity might differ between axons, the coefficient of variation of particle velocity in separate fibers tended to remain constant.The temperature dependence of mean particle velocity (V) could be adequately described by the relationship V = 0.26 exp 0.073T – 0.33, where V is in micrometres per second and T is degrees Celsius. Throughout the temperature range at which transport took place (approximately 5–35 °C) the coefficient of variation of particle velocity remained approximately constant at 0.40. All particles ceased their motion abruptly, and to some extent reversibly, at 37 °C. On morphological evidence, none of the effects of temperature appeared to be related to microtubule depolymerization.The results indicate that retrogradely transported particles with a wide range of velocities respond homogeneously to temperature changes. This supports the view that a common mechanism may underlie the motion of all the particles. No evidence was obtained that the differences between axons at room temperature could be attributed to the presence in separate axons of dissimilar proportions of faster and slower particles. Nor was the velocity–temperature characteristic in the region of room temperature sufficiently steep to explain the differences between axons. It is suggested that axons may differ in general mechanical or chemical properties so that the motion of all particles is affected uniformly.
Methylxanthines antagonize adenosine but not morphine inhibition in guinea pig ileum
Authors: Gallant Catherine A. , Clement John G.
Published: April 2011

In the electrically stimulated guinea pig ileum longitudinal muscle strip preparation the inhibitory actions of adenosine were antagonized by various concentrations of theophylline (12.5 and 100 µM) and 8-phenyltheophylline (4 and 20 µM). However, the inhibitory actions of morphine were not antagonized by the same concentration of theophylline and 8-phenyltheophylline. These results suggest that in the guinea pig ileum longitudinal muscle strip adenosine is not a mediator in the inhibitory actions of morphine.
Interaction of putative anxiolytic agents with central adenosine receptors
Authors: Williams Michael , Risley Edwin A. , Huff Joel R.
Published: April 2011

The benzodiazepine anxiolytics flurazepam and diazepam and CL 218872, zopiclone and two β-carboline ethyl carboxyl esters, compounds which are potent displacers of specific [3H]diazepam binding from rat brain membranes, have little or no activity in displacing [3H]2-chloroadenosine ([3H]2-CADO) from central A1-adenosine receptors. Conversely, the purine agonists, 1-N6-phenylisopropyladenosine, N6-cyclohexyladenosine, 2-chloroadenosine. and the adenosine antagonist 8-phenyltheophylline have no significant effect on [3H]diazepam binding. Etazolate (SQ 20009) and Avermectin B1a which enhance [3H]diazepam binding in vitro were also without significant effect on [3H]2-CADO binding. The lack of correlation of the activities of the compounds examined in the two binding assays is discussed in relation to the hypothesis that purine-like compounds may be involved in the molecular mechanisms related to anxiolytic action at the receptor level.
Effects of extracellular calcium on low frequency induced potentiation and habituation in the in vitro hippocampal slice preparation
Authors: Turner R. W. , Miller J. J.
Published: April 2011

The electrophysiological characteristics of frequency potentiation and habituation were investigated in two afferent systems of the in vitro hippocampal slice preparation. Low frequency stimulation (1 Hz) of the Schaffer collateral – commissural (Sch–comm) fibers results in a short-term potentiation of the amplitude and rate of rise of the EPSP and population spike responses recorded in the CA1 region. In contrast, 1-Hz stimulation of the perforant path (PP) evokes a short-term, habituation-like depression of the dentate granule cell EPSP and population spike. An inverse relationship was observed between stimulus intensity and the magnitude of frequency potentiation or habituation. Changes in afferent fiber volleys or general excitability of postsynaptic membranes did not contribute significantly to the development of either of these forms of short-term plasticity. Perfusion with a medium containing a high calcium – low magnesium concentration (4 mM Ca+2 and 1 mM Mg+2) produced a differential effect on CA1 and dentate evoked potentials. Following a 20-min exposure to this medium, the amplitude of CA1 potentials was increased while dentate responses were decreased. Frequency potentiation of CA1 responses and habituation of dentate responses were depressed or eliminated by the high calcium medium.The opposing influence of extracellular calcium on CA1 and dentate evoked potentials indicates a fundamental difference in the process of transmitter release in these systems, a characteristic that may contribute to the production of frequency potentiation and habituation.
Interaction of gastric inhibitory polypeptide and arginine with glucose in the perfused pancreas of rats treated with triiodothyronine
Authors: Mueller Michael K. , Pederson Raymond A. , Brown John C.
Published: April 2011

Chronic treatment of rats with triiodothyronine (T3) resulted in suppression of insulin release from the isolated pancreas when perfused with 8.6 mM glucose. This inhibition could be partially overcome by 16 mM glucose but the insulin release was still significantly reduced. Arginine and gastric inhibitory polypeptide (GIP) induced an insulinotropic action in both control and T3-treated preparations. This was achieved in the latter, in the absence of a second phase of insulin secretion to glucose. The insulinotropic effect of both arginine and GIP was abolished by mannoheptulose in both control and T3-treated animals.
The effects of some antipsychotic drugs, D-amphetamine, and reserpine on the concentration and rate of accumulation of tryptamine and 5-hydroxytryptamine in the mouse striatum
Authors: Juorio A. V.
Published: April 2011

The mouse striatum contains about 2 ng/g of tryptamine and 600 ng/g of 5-hydroxytryptamine. No significant changes in mouse striatal tryptamine were observed after the administration of chlorpromazine, haloperidol, spiperone, or α-flupenthixol. The levels of 5-hydroxytryptamine were moderately reduced by chlorpromazine, spiperone, and α-flupenthixol but not by haloperidol. The administration of antipsychotic drugs to mice pretreated with a monoamine oxidase inhibitor (pargyline) produced an increase in the rate of accumulation of striatal tryptamine compared with that of pargyline-treated mice. In contrast, the rate of accumulation of 5-hydroxytryptamine after monoamine oxidase inhibition was reduced by chlorpromazine, spiperone, and α-flupenthixol but not haloperidol. D-Amphetamine administration did not change either tryptamine or its 5-hydroxyderivative while reserpine increased tryptamine and reduced 5-hydroxytryptamine. The results suggest that changes in striatal tryptamine may be controlled by the availability of tryptophan, the amino acid precursor of tryptamine.
Effect of acetazolamide and furosemide on the production and composition of cerebrospinal fluid from the cat choroid plexus
Authors: Melby James M. , Miner Lewis C. , Reed Donal J.
Published: April 2011

The effect of acetazolamide and furosemide on choroid plexus (CP) production and electrolyte composition of cerebrospinal fluid (CSF) from the cat CP in situ was investigated. Both drugs decreased CSF production by the CP by 50–90% from a control rate of 0.53 μL ∙ min−1 ∙ mg−1 CP within 1.5–2.5 h after the start of drug treatment. The results were similar whether the drug was administered intravenously or applied directly to the CSF side of the CP. A number of experiments in which the effect of administering drugs via the chamber were studied were continued with the drugs removed by washing the preparation with drug-free artificial CSF and the responses measured. The results demonstrated that the effects of acetazolamide and furosemide were reversed during the 1st h following the washout. Both drugs decreased K concentration of nascent CSF when administered intravenously and furosemide also did so when administered on the CSF side of the CP. It is concluded from these and previous data that acetazolamide and furosemide markedly inhibit the transport mechanism(s) in the cat CP that are responsible for CP secretion which represents about 40–60% of the total CSF production and that K transport is also affected.
Sugar transport regulation in avian red blood cells: role of Ca2+ in the stimulatory effects of anoxia, adrenaline, and ascorbic acid
Authors: Bihler I. , Charles P. , Sawh P. C.
Published: April 2011

Membrane transport of sugar and Ca2+ was studied in pigeon erythrocytes by measuring the cell to medium distribution of 3-O-[14C]methyl-D-glucose and 45Ca. We have found that stimulation of sugar transport by anoxia, adrenaline, or ascorbic acid was not dependent on external Ca2+, nor was it additive to the stimulatory effect of the calcium ionophore A23187. Stimulation by ascorbic acid was dependent on concentration and time. The slow basal 45Ca efflux was greatly accelerated by A23187, and this was further increased by adrenaline. A metabolic substrate mixture consisting of adenine, inosine, and fumarate (AIF) did not alter 45Ca efflux, except for antagonizing the effect of adrenaline in the presence of A23187. Sugar transport, whether basal or stimulated by adrenaline or ascorbic acid, was significantly decreased by AIF, independently of external Ca2+. Stimulation by A23187 in the absence of external Ca2+ was also antagonized by AIF. In cells depleted of Ca2+ by treatment with A23187 and EGTA, transport stimulation by adrenaline was abolished. These results suggest that release of Ca2+ from intracellular storage into the cytoplasm plays a role in the stimulation of sugar transport by adrenaline and anoxia and also by A23187 in the absence of external Ca2+. The data provide further indirect support for a calcium-dependent mechanism of sugar transport regulation in nucleated erythrocytes.
A hypertensive substance in erythrocytes of spontaneously hypertensive rats
Authors: Wright G. L. , Bookout C.
Published: April 2011

The effect of the subcutaneous injection of plasma or erythrocytes on the blood pressure of Sprague–Dawley (S–D), Wistar–Kyoto (WKy), and spontaneously hypertensive (SH) rats was examined over a 3-week period. The injection of plasma produced no detectable alteration in blood pressure in either the normotensive or hypertensive strains. The injection of red cells from WKy rats had no effet on the blood pressure of S–D rats, whereas a moderate (20%) elevation was noted in WKy and SH rats which received erythrocytes from S–D and WKy rats, respectively. The injection of red cells from SH rats produced no effect on S–D rats, a moderate (20%) elevation of the blood pressure of WKy rats, and a marked (42%) increase in the blood pressure of SH rats. Despite the lack of effect of erythrocytes on the resting blood pressure of S–D rats, it was found that these animals exhibit a transient increase in the blood pressure response to norepinephrine (NE) following a single injection of SH red cells.The results suggest the presence of a substance in SH erythrocytes which enhances the pressor response to NE and produces an elevation of resting blood pressure. This substance also appears to occur to some extent in the red cells of S–D and WKy animals; the manifestation of its action on blood pressure elevation is determined to a significant degree by the intrinsic resistance or susceptibility of the animal.
Modulation of synapse RC1–R15 of Aplysia californica by fiber(s) of the right connective
Authors: Tremblay J. P. , Grenon Gilles
Published: April 2011

A synapse or a synaptic cluster, here called synapse RC1–R15, can be activated by threshold stimulation of the right visceropleural connective (RC) of Aplysia californica. The activity of this synapse is recorded in cell R15 of the abdominal ganglion. Repeated threshold stimulation of this synapse at 1–2 Hz generally produces a reduction of the RC1–R15 EPSPs (synaptic depression), followed by an increase to a sustained plateau (frequency facilitation). When the rate of stimulation is reduced, a rapid increase of EPSP size (posttetanic potentiation) is seen followed by an exponential decay. In this paper, we show that suprathreshold stimulation of RC accelerates this decay. It does not modify the synaptic depression and the frequency facilitation phenomena, nor does it affect the membrane resistance and potential of cell R15. In some preparation, subthreshold stimulation of RC also reduces the PTP generated by a preceeding rapid stimulation of synapse RC1–R15. High frequency (5 Hz) subthreshold stimulation of RC also reduces the synaptic depression of synapse RC1–R15. However, the subthreshold stimulation has no effect on frequency facilitation of RC1–R15. The effect of subthreshold stimulation on PTP is often correlated with the recording of a very small EPSP (sEPSP) in cell R15. This sEPSP is barely detected at the beginning of the subthreshold train of stimuli but increases with repeated stimulation. The effects obtained with subthreshold and suprathreshold stimulation of the RC are abolished in sea water with a high concentration of Ca2+ and of Mg2+. Both types of effects are attributed to the activation of fibers in the RC (called modulating fibers) which by the intermediary of one or several postulated interneurons modulate presynaptically the transmission of synapse RC1–R15.
The monoamine oxidase and catechol-O-methyltransferase activities in the dog liver
Authors: Ong Huy , Yamaguchi Nobuharu
Published: April 2011

The activity of monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) was investigated in the liver of anesthetized dogs. The MAO activity was determined by means of the method described by Wurtman and Axelrod (1963, Biochem. Pharmacol. 12: 1439–1440) using tryptamine as a substrate. The activity of COMT was assayed with the method of Axelrod (1962, Methods in Enzymology, Vol. 5. Academic Press, New York) in the presence of epinephrine bitartrate as a substrate. The average values for the activity of MAO and COMT were found to be 57.7 nmol∙min−1∙g−1 of liver and 101.8 nmol∙min−1∙g−1 of liver, respectively. No significant difference in the enzyme activity was observed among various samples obtained from distinct zones (peripheral and central) and lobes at different time of sample collections. The results suggest the homogenous distribution of MAO and COMT in the dog liver. The striking difference in the COMT activity in the dog liver as compared with that reported by others for the cat liver is probably due to a species difference between these two animals.
Cholinergic control of canine antral immunoreactive gastrin release and motility
Authors: Fox J. E. T. , Daniel E. E. , Jury J. , Track N. S. , Chiu S.
Published: April 2011

We used acute anaesthetized dogs to investigate the role of cholinergic receptors in the relationship between antral immunoreactive (I) gastrin release and antral motility. Electrical stimulation of extrinsic nerves via the cervical vagus or the nerve of Latarjet appeared to increase I gastrin release and antral motility by separate pathways as blockade of muscarinic receptors, i.e., atropinization inhibited motility but did not alter I gastrin release. On the other hand, blockade of nicotinic receptors by hexamethonium treatment obliterated I gastrin release induced by stimulation of the extrinsic nerves but only reduced motility. Field stimulation of intrinsic nerves via serosal electrodes also increased both I gastrin release and local motility. Since hexamethonium treatment only slightly reduced both I gastrin release and motility and atropinization eliminated both during field stimulation, the presence of a muscarinic receptor in the final pathway for each is proposed.Atropine eliminated carhachol-induced I gastrin release and motility increases, even in the presence of nerve blockade by tetrodotoxin. This suggests that this muscarinic receptor is on the smooth muscle cell itself and possibly on the gastrin cell. However a proposed role of the somatostatin cell in controlling gastrin release is also consistent with these data.Thus, both an intrinsic cholinergic and a separate extrinsic noncholinergic pathway are involved in antral release of I gastrin but initiation of motility appears to involve a final common pathway terminating in a muscarinic receptor on the smooth muscle cell.
Effects of inotropic agents on arterial resistance and venous compliance in anesthetized dogs
Authors: Ogilvie R. I.
Published: April 2011

Systemic vascular effects of dopamine, dobutamine, and prenalterol were studied in 45 anesthetized open-chest dogs. Blood flow [Formula: see text] and right atrial pressure (Pra) were independently controlled by a right heart bypass. Transient changes in central blood volume after an acute reduction in Pra at a constant [Formula: see text] showed that blood was draining from two vascular compartments with different time constants, one fast and the other slow. Dopamine (2.5–10 μg∙kg−1∙min−1) was the most active drug with dose-related increases in heart rate 6–19%, arterial pressure (Pa) 3–36%, and venous compliance 2–25%. Small doses of dopamine (2.5 and 5 μg∙kg−1∙min−1) reduced arterial resistance of the slow time-constant compartment increasing [Formula: see text] distribution to that compartment 21–42%, whereas larger doses increased both arterial resistance and venous compliance in that compartment. Arterial resistance in the fast time-constant compartment increased with all doses of dopamine. Dobutamine (2.5–10 μg∙kg−1∙min−1) modestly increased heart rate 2–11% and Pa 9–12%) without altering [Formula: see text] distribution demonstrating a relatively flat dose response. Dobutamine 2.5–5 μg∙kg−1∙min−1 increased venous compliance 5–10% while 10 μg∙kg−1∙min−1 had no effect or decreased compliance of both compartments. Prenalterol 3 μg∙kg−1∙min−1 increased Pa 9% primarily by increasing arterial resistance in the fast time-constant compartment without altering heart rate or blood flow distribution. Doses of prenalterol 10–100 times greater caused dose-dependent reductions in Pa and vascular compliance. In this animal model of the circulation with a fixed cardiac output, dopamine had the greatest effect on the peripheral vasculature and chronotropy.
Studies on the interaction of Escherichia coli endotoxin with erythrocyte membranes
Authors: Godin David V. , Tuchek John M. , Garnett Maureen E.
Published: April 2011

Escherichia coli lipopolysaccharide (endotoxin) alters the stability of erythrocytes to hypotonic lysis although the nature and magnitude of the effect varied with temperature and with the type of red blood cell examined. Evidence has been obtained suggesting a possible modulatory role of membrane lipids in governing the molecular consequences of membrane–endotoxin interaction. The marked effect of temperature on the stabilization of red cells by endotoxin was not attributable to variations in toxin binding and was not observed with more conventional structurally unrelated antihemolytic agents. Although chemical modifications which alter the toxicity of endotoxin in vivo also modify its ability to stabilize erythrocytes in vitro, no simple relationship between in vivo endotoxin toxicity and in vitro effects on erythrocyte stability was apparent. The critical dependence of endotoxin antihemolytic effects in vitro on molecular structure may offer a convenient means of assessing the homogeneity of these preparations before performing experiments in vivo.
Nonspecific proteases: a new approach to the isolation of adult cardiocytes
Authors: Bustamante J. Omar , Watanabe Toshifumi , McDonald Terence F.
Published: April 2011

The potent collagenolytic activity of nonspecific proteinases suggested their use as enzymatic agents for the dissociation of single adult heart cells. This was assessed in guinea pig hearts perfused for 1 min with solutions containing hyaluronidase (100–10000 U/mL), trypsin (100–10000 U/mL), crude collagenase (100–500 U/mL), or nonspecific protease (0.1–100 U/mL). No rod-shaped cells were observed among the cells isolated with these concentrations of hyaluronidase, trypsin, or crude collagenase. By contrast, 45–80% of the cells released with nonspecific protease (5–10 U/mL) were rod shaped and Ca2+ tolerant. Resting and action potentials recorded from cells dispersed with nonspecific protease were similar to those recorded from cells isolated after prolonged collagenase exposure.
Alterations in the heme biosynthetic pathway as an index of exposure to toxins
Authors: Marks Gerald S. , Zelt David T. , Cole Susan P. C.
Published: April 2011

Under normal circumstances the heme biosynthetic pathway is carefully controlled and porphyrins are formed in only trace amounts. When control mechanisms are disturbed by xenobiotics, porphyrins may be formed and serve as a signal of the interaction between a xenobiotic and the heme biosynthetic pathway. For example, porphyrinuria was an early manifestation of a hexachlorobenzene-induced porphyria outbreak in Turkey. In humans exposed to polybrominated biphenyls and to 2,3,7,8-tetrachlorodibenzo-p-dioxin the urinary porphyrin pattern was significantly different from normal in a large number of exposed individuals. The question is raised whether measurement of urinary porphyrin profiles by improved methods will enable an estimate to be made of the extent of exposure to haloaromatic hydrocarbons in the human population. A wide variety of xenobiotics interact with the prosthetic heme of cytochrome P-450 forming novel N-alkylporphyrins. Identification of these N-alkylporphyrins in body fluids might provide a means of assessing exposure to a variety of xenobiotics in human populations.